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Nitrazepam chemical structure
| CAS number |
| ATC code |
| PubChem |
| DrugBank |
|Molecular weight||281.3 g/mol|
|Elimination half-life||16-38 hours|
|Legal status||Schedule IV (International)|
|Routes of administration||Oral|
Nitrazepam (marketed under the trade names Mogadon, Alodorm, Hypnotex, Remnos, Pacisyn, Eunoctin and Pelson) is a type of benzodiazepine drug. It is a powerful hypnotic drug which possesses strong sedative and motor impairing properties. Nitrazepam also has anxiolytic, amnestic, anticonvulsant, and skeletal muscle relaxant properties.
Nitrazepam is most often used to treat short-term sleeping problems (insomnia). Insomnia can be described as a difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Nitrazepam is a long acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep. Intermediate half life benzodiazepines are also useful for patients with difficulty in maintaining sleep eg loprazolam, lormetazepam, temazepam. Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis. Nitrazepam shortens the time required to fall asleep and lengthens the duration of sleep. It is also useful for the management of myoclonic seizures.
Nitrazepam is categorised as a nitrobenzodiazepine. Other nitrobenzodiazepines include flunitrazepam and clonazepam. Nitrobenzodiazepines are metabolised to a 7-amino-metabolite. Nitrazepam is classed as a 1,4 benzodiazepine, with the chemical name 1,3-Dihydro-7-nitro-5-phenyl-2H-1,4- -benzodiazepin-2-one.
It is a long acting benzodiazepine, is lipophilic and is metabolised hepatically via oxidative pathways. The main pharmacological effects of nitrazepam are the enhancement of GABA at the GABAA receptor. It is a full agonist of the benzodiazepine receptor. An opioid mechanism of action may play a role in some of the pharmacological properties of nitrazepam. Nitrazepam causes a decrease in the cerebral contents of the amino acids glycine and aspartic acid. The decrease may be due to activation of benzodiazepine receptors. At high doses decreases in histamine turnover occur as a result of nitrazepam's action at the benzodiazepine-GABA receptor complex. Nitrazepam possesses antipruritic properties. The antipruritic properties of nitrazepam are believed to be due to a central mechanism of action rather than a peripheral mechanism of action. Nitrazepam has demonstrated cortisol suppressing properties. Nitrazepam is structurally related to quinazolines and is a hapten.
Nitrazepam and other benzodiazepines may influence neurosteroid metabolism and progesterone levels which in turn may influence the functions of the brain and reproductive system. Nitrazepam and medazepam were found to have the strongest effects on neurosteroids and progesterone. The pharmacological actions of benzodiazepines at the GABAa receptor are similar to those of neurosteroids. Neuroactive steroids are positive allosteric modulators of the GABAa receptor, enhancing GABA function. Many benzodiazepines (diazepam, medazepam, estazolam, temazepam, flunitrazepam and nitrazepam) potently inhibit the enzymes involved in the metabolism of neurosteroids. Long-term administration of benzodiazepines may influence the concentrations of endogenous neurosteroids, and thereby would modulate the emotional state. Factors which effects the ability of individual benzodiazepines to alter neurosteroid levels depend on the molecular make up of the individual benzodiazepine drug. Presence of a substituent at N1 position of the diazepine ring and/or the chloro or nitro group at position 7 of the benzene ring contribute to potent inhibition of the isoenzymes, and in turn a bromo group at position 7 (for bromazepam) and additional substituents (3-hydroxy group for oxazepam and tetrahydroxazole ring for cloxazolam and oxazolam) decrease the inhibitory potency of benzodiazepines on neurosteroids. Nitrazepam also induces melanogenesis in melanoma cells via modulating cell differentiation.
EEG and sleepEdit
In sleep laboratory studies, nitrazepam decreased sleep latency. However, in a clinical study nitrazepam was found to be no more effective than placebo tablets in increasing total time spent asleep, was found to significantly impair trial subjects abilities to move and carry out everyday activities the next day and it was concluded that nitrazepam should not be used as a sleep aid.
Stage 2 NREM sleep is significantly increased by nitrazepam but SWS stage sleep is significantly decreased by nitrazepam. There is delay in the onset, and decrease in the duration of REM sleep. Following discontinuation of the drug, REM sleep rebound has been reported in some studies. Nitrazepam is reported to significantly affect stages of sleep: a decrease stage 1, 3 and 4 sleep and to increase stage 2. In young volunteers the pharmacological properties of nitrazepam was found to produce sedation, impaired psychomotor performance and standing steadiness. EEG tests showed a decrease of alpha activity and increased the beta activity. These effects increased according to blood plasma levels of nitrazepam. Performance was significantly impaired 13 hours after dosing with nitrazepam as was decision-making skills. EEG tests show more drowsiness and light sleep 18 hours after nitrazepam intake more so than amylobarbitone. Fast activity was recorded via EEG 18 hours after nitrazepam dosing. An animal study demonstrated that nitrazepam induces a drowsy pattern of spontaneous EEG including high voltage slow waves and spindle bursts increase in the cortex and amygdala, while the hippocampal theta rhythm is desynchronized. Also low voltage fast waves occur particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus is significantly suppressed. The photic driving response elicited by a flash light in the visual cortex is also suppressed by nitrazepam. Estazolam was found to be more potent however. Nitrazepam increases the slow wave light sleep (SWLS) in a dose-dependent manner whilst suppressing deep sleep stages. Less time is spent in stages 3 and 4 which are the deep sleep stages when benzodiazepines such as nitrazepam are used. Benzodiazepines are therefore not good hypnotics in the treatment of insomnia. The suppression of deep sleep stages by benzodiazepines may be especially problematic to the elderly as they naturally spend less time in the deep sleep stage.
Nitrazepam produces a decrease in delta activity and an increase in the total non-REM sleep time and a decrease in delta activity during non-REM sleep. The effect of benzodiazepine drugs on delta however may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep. Delta activity is thought to reflect sleep quality with lower levels of delta sleep reflecting poorer quality of sleep. Thus nitrazepam and other benzodiazepines cause a deterioration in sleep quality. Cyproheptadine may be superior to nitrazepam in the treatment of insomnia.
Nitrazepam is largely bound to plasma proteins. Benzodiazepines such as nitrazepam are lipid soluble and have a high cerebral uptake. The time for nitrazepam to reach peak plasma concentrations following oral administration is about 2 hours (0.5 to 5 hours). Nitrazepam breaks down into a nitro benzophenone and quinolone compound. The half life which is the time taken for a dose to decrease by half is 16.5 to 48.3 (mean 28.8) hours. Both low dose (5 mg) and high dose (10 mg) of nitrazepam significantly increases growth hormone levels in humans. Nitrazepam has a much longer half life in the cerebrospinal fluid. The half life in the cerebrospinal fluid is 68 hours which indicates that nitrazepam is eliminated extremely slowly from the cerebrospinal fluid. Nitrazepam has a half life of about 29 hours in young people and a much longer half life in the elderly. In the elderly the half life is about 40 hours. Concomitant food intake has no influence on the rate of absorption of nitrazepam nor on its bioavailability. Therefore nitrazepam can be taken with or without food.
Mechanism of actionEdit
Nitrazepam belongs to a group of medicines called benzodiazepines. It acts on benzodiazepine receptors in the brain which are associated with the GABA receptors causing an enhanced binding of GABA (gamma amino butyric acid) to GABAA receptors. GABA is a major inhibitory neurotransmitter in the brain, involved in inducing sleepiness, muscular relaxation and control of anxiety and fits, and slows down the central nervous system. The mechanism of action of nitrazepam is the same as other benzodiazepine drugs and zopiclone. The anticonvulsant properties of nitrazepam and other benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation. The muscle relaxant properties of nitrazepam are produced via inhibition of polysynaptic pathways in the spinal cord.
Nitrazepam possesses potent anti-epileptic properties and has been used in the management of seizure disorders in children and also for infantile spasms. Clonazepam has also been used for the same indications. However, the usefulness of nitrazepam and clonazepam is limited due to their deliterious effect on neurological function, especially their negative effect on cognition. Clobazam a 1,5-benzodiazepine has shown to be less neurotoxic than 1,4-benzodiazepines such as nitrazepam and clonazepam.
Nitrazepam is sometimes used for refractory epilepsies. However, long term prophylactic treatment of epilepsy has considerable drawbacks. Most importantly the loss of antiepileptic effects due to tolerance which renders prolonged nitrazepam therapy ineffective. Nitrazepam also has the draw back of significant side effects such as sedation, which is why nitrazepam and benzodiazepines in general are only prescribed in the acute management of epilepsies. Nitrazepam has been found to be more effective than clonazepam in the treatment of west syndrome which is an age dependent epilepsy, affecting the very young. However, as with other epilepies treated with benzodiazepines, long term therapy becomes ineffective with prolonged therapy and the side effects of hypotonia and drowsiness are troublesome with nitrazepam therapy, other antiepileptic agents are therefore recommended for long term therapy, possibly Corticotropin (ACTH) or vigabatrin.
Nitrazepam along with diazepam, oxazepam and temazepam represent 82% of the benzodiazepine market in Australia. The rate of benzodiazepine prescribing in Tasmania is higher than in Australia. Nitrazepam and flunitrazepam prescribing levels in Tasmania are disturbingly high. Prescribing of hypnotics in Norway is quite restrictive with only 3 hypnotics which are prescribable; nitrazepam, flunitrazepam and zopiclone. The usage of benzodiazepine hypnotics in local authority homes for the elderly established via a clinical survey that 34% of residents were taking sleeping medication. However, the number varied between the homes with some homes reporting only 2.3% of residents to be on hypnotic medication and others up to 56.5% on hypnotic drugs. Nitrazepam was the most frequently prescribed hypnotic medication accounting for a third of hypnotic use.
When used for treatment of insomnia, the usual dose for adults is 2.5mg to 10mg, taken at bedtime. Typically, it works within the hour and allows the individual to maintain sleep for 4 to 8 hours. When used for treatment of myoclonic seizures, the dose is based on body weight. The dose for children (30kg or less) is anywhere from 0.3mg/kg to 1mg/kg, daily in three divided doses.
Tolerance to a drugs effects occurs after regular exposure to a drug. The mechanism of nitrazepam tolerance may be due to down-regulation of benzodiazepine receptors. When tolerance and habituation occurs to nitrazepam its pharmacokinteic profile changes with absorption of the drug slowing down, elimination time increasing and brain concentration of nitrazepam increasing significantly. Increased levels of GABA in cerebral tissue and alterations in the activity state of the serotoninergic system occurs as a result of nitrazepam tolerance.
Although tolerance to the sleep inducing properties of nitrazepam develops within a matter of days so to does tolerance to the residual performance impairment. After 6 days of use tolerance to nitrazepam's sleep inducing effects and performance impairing effects occurs. One study demonstrated tolerance to the sleep promoting effects of nitrazepam and temazepam after 7 days nightly administration. Quality of sleep was found to be increased after the first nights administration of either nitrazepam or temazepam but by day 7 quality of sleep was found to have returned to baseline suggesting the development of complete tolerance after 7 days use. In mice tolerance to the anticonvulsant properties of nitrazepam developed profoundly and rapidly over 6 days, although some anticonvulsant effects were still apparent after 6 days administration. In humans tolerance to the anticonvulsant effects of nitrazepam is a frequent occurance.
See also benzodiazepine withdrawal syndrome
Benzodiazepine drugs such as nitrazepam can cause dependence and addiction and is what is known as the benzodiazepine withdrawal syndrome. Withdrawal from nitrazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen with alcohol and barbiturates. The higher the dose and the longer the drug is taken the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can however occur at standard dosages and also after short term treatment. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regime.
Frequent use of nitrazepam may cause dependence and when the drug is reduced or stopped, withdrawal symptoms. Withdrawal symptoms including a worsening of insomnia compared to baseline typically occurs after discontinuation of nitrazepam even after short term single nightly dose therapy. Dependence on benzodiazepines such as nitrazepam or temazepam often occurs due to discharging patients from hospital on benzodiazepines who were started on benzodiazepine hypnotics in hospital. It is recommended that hypnotic use in hospital be limited to 5 days to avoid the development of drug dependence and withdrawal insomnia.
After discontinuation of nitrazepam a rebound effect may occur about 4 days after stopping medication. Nitrazepam has more side effects than other hypnotic drugs and tolerance to sedative properties and rebound insomnia after discontinuation occurs after only 7 days administration. Tolerance to the anticonvulsant and anxiolytic effects also develops rapidly during daily administration.
Abrupt withdrawal after long term use from therapeutic doses of nitrazepam may result in a severe benzodiazepine withdrawal syndrome. Reports in the medical literature report of two psychotic states developing after abrupt withdrawal from nitrazepam including delirium after abrupt withdrawal of 10 mg of nitrazepam and in another case auditory hallucinations and visual cognitive disorder developed after abrupt withdrawal from 5 mg of nitrazepam and 0.5 mg of triazolam. Gradual and careful reduction of the dosage was recommended to prevent severe withdrawal syndromes from developing. Antipsychotics increase the severity of benzodiazepine withdrawal effects with an increase in the intensity and severity of convulsions. Depersonalisation has also been reported as a benzodiazepine withdrawal effect from nitrazepam.
Abrupt withdrawal from very high doses is even more likely to cause severe withdrawal effects. Withdrawal from very high doses of nitrazepam may cause severe hypoperfusion of the whole brain with diffuse slow activity on EEG. After withdrawal, abnormalities in hypofrontal brain wave patterns may persist beyond the withdrawal syndrome suggesting that organic brain damage may occur from chronic high dose abuse of benzodiazepines.
The Committee on the Review of MedicinesEdit
The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence and benzodiazepine withdrawal problems and other adverse effects. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are therefore unsuitable treatments for conditions such as depression, tension headaches and dysmenorrhoea. Benzodiazepines are also not beneficial in the treatment of psychosis due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of anxiety or insomnia in children. The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there was little evidence that long term use of benzodiazepine hypnotics were benefitial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 - 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 - 10 days after the cessation of a more long acting benzodiazepine. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels. However, withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was also noted in the review that alcohol can potentiate the central nervous system depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous. The elderly are more prone to these adverse effects. In the neonate high single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia and irregularities in the fetal heart. Benzodiazepines should be avoided in lactation. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhoea. In the case of nitrazepam it was recommended that nitrazepam only be used for the short term treatment of insomnia where day time sedation was acceptable.
Aromatic nitro-containing compounds such as nitrazepam produce superoxide free radicals during cellular metabolism by endothelial cells. Nitrazepam is much more toxic than other benzodiazepines probably due to its extensive nitro reduction to 7-aminonitrazepam free radical by intestinal microflora. Nitrazepam a nitro-containing benzodiazepine is reduced by NADPH-cytochrome c (P-450) reductase to a nitro anion free radical and in the presence of oxygen, superoxide is generated. It was found that nitrazepam produced superoxide intracellularly but not extracellulary. Free radicals such as superoxide injure and degenerate the cell integrity of cells. Nitrazepam undergoes enterocyte metabolism to form oxidative free radicals. Superoxide is intracellularly produced during nitrazepam metabolism and this oxidative metabolism can lead to cellular dysfunction. Superoxide is generated by the one electron reduction of nitrazepam to its corresponding nitro anion free radical during drug metabolism.
Nitrazepam is carcinogenic and has been found to be both photogenotoxic and photocytotoxic. Studies on animals have demonstrated teratogenic and also carcinogenic effects of nitrazepam and some other benzodiazepines and the wide spread use of these drugs world wide is of major concern for human health.
Nitrazepam has been reported in the medical literature by researchers as a drug which is well known for inducing testicular and reproductive toxicities. Nitrazepam decreases the number of motile sperm, curilinear velocity, beat cross frequency, maximum and mean amplitude of lateral head displacement and causes testicular lesions. Nitrazepam may result in low fertility.
In studies of rats, nitrazepam induced reproductive toxicity has been demonstrated after 2 weeks of therapy, with significant decreases in fertility in nitrazepam treated male rats. Testicular signs of toxicity, decrease in number of sperm heads in the testis and increase in number of sperm with abnormal heads was found after 2 weeks treatment with high dose nitrazepam and after 4 weeks in the lower dosed rats. Nitrazepam has also been shown at high doses to affect sperm motion in laboratory tests via causing lesions in spermatids.
Nitrazepam has been shown in rats to cause testicular damage. A decrease in the weight of the testis, weight of the epididymis, number of sperm in the testis and sperm motility was shown in moderate and high dose nitrazepam treated rats. Rats treated with high doses of nitrazepam show a significant decrease in pregnancy rate. Localised necrosis in the seminiferous epithelium and Leydig cell hyperplasia occurs in the testis of rats treated with nitrazepam and morphological changes occur in spermatocytes with necrosis of the cytoplasm. Laboratory tests assessing the toxicity of nitrazepam, diazepam and chlordiazepoxide on mice spermatozoa found that nitrazepam produced the most toxicities on sperm including abnormalities involving both shape and size of the sperm head.
In female rats nitrazepam has been shown to inhibit ovulation.
In a rat study Nitrazepam showed much greater damage to the fetus, as did nimetazepam and temazepam than other benzodiazepines. High levels of nitrazepam were found in the maternal serum and in the whole fetus which may account for the increased toxicity. Diazepam showed relatively weak fetal toxicities. Rats treated with a single very high dose of nitrazepam on day 12 of gestation significant increase in malformation in rats. However, mice seem more resistant to the teratogenic effects which may be related to differences in metabolism of nitrazepam between the two species. Exencephaly, cleft palate, micrognathia, short or kinky tail and limb reduction defects occurred in rats treated with a single very high dose of nitrazepam, with limb buds revealing hemorrhage and mesenchymal cell necrosis. Another fetal toxicity study in rats demonstrated that nitrazepam has embryocidal activity in vitro. Nitrazepam possesses both embryotoxicity and teratogenicity toxicities in vivo.
Nitrazepam therapy compared with other drug therapies increases risk of death when used for intractable epilepsy in an analysis of 302 patients. The risk of death from nitrazepam therapy may be greater in younger patients with intractable epilepsy. Nitrazepam may cause sudden death. Nitrazepam therapy can cause swallowing incoordination, high-peaked esophageal peristalsis, bronchospasm, delayed cricopharyngeal relaxation and severe respiratory distress necessitating ventilatory support. Nitrazepam may promote the development of parasympathetic overactivity or vagotonia leading to potentially fatal respiratory distress.
Nitrazepam was the most commonly detected benzodiazepine in urine samples in the UK in 1997 suggesting a high liking and preference amongst drug abusers. However, it has been superseded by temazepam, despite the fact that temazepam is much more highly regulated in the UK. Temazepam is Class B drug, while nitrazepam is a Class C drug. In Nepal, nitrazepam is a major drug of abuse as is codeine, heroin, buprenorphine and cannabis.
Nitrazepam in animal studies has been shown to increase reward seeking which may suggest increased risk of addictive behavioural patterns. Studies suggest that nitrazepam caused significant euphoria as against placebos and was identified as an active drug by the subjects. Nitrazepam resembled diazepam (Valium), however, on certain parameters the effects produced by nitrazepam were more pronounced. Nitrazepam was found to be an abusable drug and has similar abuse liability like diazepam, if not slightly higher. Treatment with nitrazepam should usually not exceed 7 to 10 consecutive days. Use for more than 2 to 3 consecutive weeks requires complete re-evaluation of the patient. Prescriptions for nitrazepam should be written for short-term use (7 to 10 days) and it should not be prescribed in quantities exceeding a 1-month supply. Dependence can occur in as little as four weeks.
Benzodiazepines, including diazepam, temazepam, nitrazepam and flunitrazepam account for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines, suggesting benzodiazepines are a major prescription drug class of abuse.
Nitrazepam is detected frequently in cases of people suspected of driving under the influence of drugs in Sweden. Other benzodiazepines and zolpidem and zopiclone are also found in high numbers in suspected impaired drivers. Many drivers have blood levels far exceeding the therapeutic dose range suggesting a high degree of abuse potential for benzodiazepines and zolpidem and zopiclone. In Northern Ireland in cases where drugs were found in tests on impaired drivers, benzodiazepines were found to be present in 87% of cases.
Cognitive Behavioural TherapyEdit
Nitrazepam, temazepam and zopiclone are the most frequently prescribed hypnotics in the United Kingdom. Hypnotic drugs are of poor value for the management of chronic insomnia. Hypnotic drug consumption has been shown to reduce work performance, increase absenteeism, increase road traffic accidents, increased morbidity, increase mortality and is associated with an increased incidence of deliberate self harm. In the elderly, increases in falls and fractures associated with sedative hypnotic drug use has been found. It is widely accepted that hypnotic drug usage beyond 4 weeks is undesirable for all age groups of patients. Many continuous hypnotic users exhibit disturbed sleep as a consequence of tolerance but experience worsening rebound or withdrawal insomnia when the dose is reduced too quickly which compounds the problem of chronic hypnotic drug use. Cognitive behavioural therapy has been found to be more effective for the long term management of insomnia than sedative hypnotic drugs. No formal withdrawal programs for benzodiazepines exists with local providers in the UK. Meta-analysis of published data on psychological treatments for insomnia show a success rate between 70 and 80%. A large scale trial utilising cognitive behavioural therapy in chronic users of sedative hypnotics including nitrazepam, temazepam and zopiclone found CBT to be a significantly more effective long term treatment for chronic insomnia than sedative hypnotic drugs. Persisting improvements in sleep quality, sleep latency, increased total sleep, improvements in sleep efficiency, significant improvements in vitality, physical and mental health at 3, 6 and 12 month follow up was found in those receiving cognitive behavioural therapy. A marked reduction in total sedative hypnotic drug use was found in those receiving CBT, with 33% reporting zero hypnotic drug use. Age has been found not to be a barrier to successful outcome of CBT. It was concluded that CBT for the management of chronic insomnia was flexible, practical and a cost effective treatment and it was also concluded that CBT leads to a reduction of benzodiazepine drug intake in a significant number of patients.
Common Side EffectsEdit
CNS depression including, somnolence, dizziness, depressed mood, rage, violence, fatigue, ataxia, headache, vertigo, impairment of memory, impairment of motor functions, hangover feeling in the morning, slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, double vision and inattention have been reported. Unpleasant dreams and rebound insomnia has also been reported. High levels of confusion, clumsiness also occurs after administration of nitrazepam. Increased reaction time, co-ordination problems and impaired learning and memory.
Impaired learning and memory occurs due to the action of the drug on benzodiazepine receptors which causes a dysfunction in the cholinergic neuronal system. Nitrazepam causes a reduced output of serotonin which is closely involved in regulating mood and may be the cause of feelings of depression in users of nitrazepam or other benzodiazepines.
Nitrazepam is a long acting benzodiazepine with an elimination half life of 15-38 (mean elimination half life 26 hours). Residual 'hangover' effects after nighttime administration of nitrazepam such as sleepiness, impaired psychomotor and cognitive functions may persist into the next day which may impair the ability of users to drive safely and increases the risk of falls and hip fractures. Significant impairment of visual perception and sedative effects persisting into the next day typically occurs with nitrazepam administration as was demonstrated in a human clinical trial assessing the effect of nitrazepam on peak saccade velocity.
Impairment of psychomotor function may especially occur after repeated administration, with the elderly being more vulnerable to this adverse effect. Overall accuracy of completing tasks is impaired after repeated administration of nitrazepam and is due to drug accumulation of nitrazepam. The elderly are more vulnerable to these side effects.
Less Common Side EffectsEdit
Hypotension, faintness, palpitation, rash or pruritus, gastrointestinal disturbances, changes in libido. Very infrequently, paradoxical reactions may occur, e.g. excitement, stimulation, hallucinations, hyperactivity and insomnia. Also depressed or increased dreaming, disorientation, severe sedation, retrograde amnesia, headache, hypothermia, delirium tremens. Acroparaesthesia has been reported as a side effect from nitrazepam with symptoms including, pins and needles in hands and loss of power of fingers and clumsiness of the fingers.
Nitrazepam interacts with the antibiotic erythromycin which is a strong inhibitor of CYP3A4, which affects concentration peak time. This interaction is not to believed to be clinically important. However, anxiety, tremor and depression have been documented in a case report following administration of nitrazepam and triazolam. Following administration of erythromycin to the patient, repetitive hallucinations and abnormal bodily sensations developed. The patient had however acute pneumonia and renal failure. Co-administration of benzodiazepine drugs at therapeutic doses with erythromycin may cause serious psychotic symptoms especially in those with other significant physical complications. Oral contraceptive pills, reduce the clearance of nitrazepam which may lead to increased plasma levels of nitrazepam and accumulation. Rifampin increases the clearance of nitrazepam significantly and probenecid decreases the clearance of nitrazepam significantly. Cimetidine slows down the elimination rate of nitrazepam leading to more prolonged effects of nitrazepam and increased risk of accumulation. Alcohol (ethanol) in combination with nitrazepam may cause a synergistic enhancement of the hypotensive properties of both benzodiazepines and alcohol. Benzodiazepines including nitrazepam may inhibit the glucuronidation of morphine leading to increased levels of and prolongation of the effects of morphine.
It has been recommended in the medical literature that caution should be exercised in prescribing nitrazepam to anyone who is of working age due to the significant impairment of psychomotor skills. This impairment is greater the higher the dosage that is prescribed. Nitrazepam in doses of 5 mg or more causes significant deterioration in vigilance performance combined with increased feelings of sleepiness. Doses as low as 5 mg of nitrazepam can impair driving skills. Therefore people driving or conducting activities which require vigilance should exercise caution in using nitrazepam or possibly avoid it all together.
Caution in the elderly. Nitrazepam has been found to be dangerous in elderly patients due to a significant increased risk of falls. This increased risk is probably due to the persisting drug effects of nitrazepam well into the next day. Nitrazepam is a particularly unsuitable hypnotic for the elderly as it induces a disability characterised by general mental deterioration, inability to walk, incontinence, dysarthric, confusion, prone to stumbling, falls and disoriention which can occur from doses as low as 5 mg. The nitrazepam induced symptomatology can lead to a misdiagnosis of brain disease in the elderly eg dementia and can also lead to the symptoms of postural hypotension which may also get misdiagnosed. It was reported that a geriatric unit was seeing as many as 7 patients a month with nitrazepam induced disabilities and health problems. It was recommended that nitrazepam should join the barbiturates in not being prescribed to the elderly. Only nitrazepam and lorazepam were found to increase the risk of falls and fractures in the elderly. CNS depression occurs much more frequently in the elderly and is especially common in doses above 5 mg of nitrazepam. Both young and old patients report sleeping better after 3 nights use of nitrazepam however they also report feeling less awake and are slower on psychomotor testing up to 36 hours after intake of nitrazepam. The elderly showed cognitive deficits, making significantly more mistakes in psychomotor testing than younger patients despite similar plasma levels of the drug, suggesting that the elderly are more sensitive to nitrazepam due to increased sensitivity of the aging brain to nitrazepam. Confusion and disorientation can result from chronic nitrazepam administration to elderly subjects. Also the effects of a single dose of nitrazepam may last up to 60 hours after administration.
Caution in children. Nitrazepam is not recommended for use in those under 18. Use in very young children may be especially danagerous. Nitrazepam was implicated, along with the drugs diphenylhydantoin and clonazepam, in the death of a 7 and a half month old girl. She developed inclusions consisting of lamellar profiles, situated in membrane-bound cytosomes which were found mainly in astrocytes, but also in neurones and in the axons of peripheral nerves before dying. Lipofuscin bodies were also found to be increased in number. Children treated with nitrazepam for epilepsies may develop tolerance within months of continued use, with dose escalation often occurring with prolonged use. Sleepiness, deterioration in motor skills and ataxia were common side effects in children with tuberous sclerosis treated with nitrazepam. The side effects of nitrazepam may impair the development of motor and cognitive skills in children treated with nitrazepam. Withdrawal of nitrazepam only occasionally resulted in a return of seizures and some children withdrawn from nitrazepam appeared to improve. Development, eg able to walk at 5 years was impaired in many children taking nitrazepam but was not impaired with several other non benzodiazepine antiepileptic agents. It has been recommended that children being treated with nitrazepam should be reviewed and have their nitrazepam gradually discontinued whenever appropriate.
Caution in hypothyroidism. Caution should be exercised by people who have hypothyroidism as this condition may cause a long delay in the metabolism of nitrazepam leading to significant drug accumulation.
Nitrazepam is a long acting benzodiazepine and there is a risk of drug accumulation, even though no active metabolites are formed during metabolism. Accumulation can occur in various body organs including the heart, accumulation is even greater in babies. Nitrazepam rapidly crosses the placenta and also is present in breast milk in high quantities. Therefore nitrazepam and benzodiazepines should be avoided during pregnancy and breast feeding. In early pregnancy nitrazepam levels are lower in the baby than in the mother and in the later stages of pregnancy nitrazepam is found in equal levels in both the mother and the unborn child. Internationally benzodiazepines are known to cause harm when used during pregnancy and nitrazepam is a category D drug during pregnancy.
Benzodiazepines are lipophilic and rapidly penetrate membranes and therefore rapidly penetrate the placenta with significant uptake of the drug. Use of benzodiazepines eg nitrazepam in late pregnancy especially high doses may result in floppy infant syndrome. Use in the third trimester stage of pregnancy may result in the development of a severe benzodiome in the neonate. Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. These symptoms may persist for hours or months after birth.
Nitrazepam should be avoided in patients with chronic obstructive pulmonary disease (COPD), especially during acute exacerbations of COPD, due to the fact that serious respiratory depression may occur in patients who are receiving hypnotics.
Nitrazepam should be avoided in patients who drive or operate machinery. A study assessing driving skills of sedative hypnotic users found that users of nitrazepam were found to be significantly impaired up to 17 hours after dosing, whereas users of temazepam did not show significant impairments of driving ability. These results reflect the long acting nature of nitrazepam.
Nitrazepam is a drug which is very frequently involved in drug intoxication, including overdose. Nitrazepam overdose may result in stereotypical symptoms of benzodiazepine overdose including intoxication, impaired balance and slurred speech. In cases of severe overdose this may progress to a comatose state with the possibility of death. The risk of nitrazepam overdose is increased significantly if nitrazepam is abused in conjunction with opiates, as was highlighted in a review of deaths of users of the opiate buprenorphine. Severe nitrazepam overdose resulting in coma causes the central somatosensory conduction time (CCT) after median nerve stimulation to be prolonged and the N20 to be dispersed. Brain-stem auditory evoked potentials demonstrate delayed interpeak latencies (IPLs) I-III, III-V and I-V. Toxic overdoses therefore of nitrazepam cause prolonged CCT and IPLs.
Benzodiazepines were implicated in 39% of suicides by drug poisoning in Sweden, with nitrazepam, temazepam and flunitrazepam accounting for 90% of benzodiazepine implicated suicides, in the elderly over a period of 2 decades. In three quarters of cases death was due to drowning, typically in the bath. Benzodiazepines were the predominant drug class in suicides in this review of Swedish death certificates. In 72% of the cases benzodiazepines were the only drug consumed. Benzodiazepines and in particular temazepam, nitrazepam and flunitrazepam should therefore be prescribed with caution in the elderly. In a brain sample of a fatal nitrazepam poisoning high concentrations of nitrazepam and its metabolite were found in the brain of the deceased person.
In a retrospective study of deaths, when benzodiazepines were implicated in the deaths, the benzodiazepines nitrazepam, temazepam, and flunitrazepam were the most common benzodiazepines involved. Benzodiazepines were a factor in all deaths related to drug addiction in this study of causes of deaths. Nitrazepam, temazepam, and flunitrazepam were significantly more commonly implicated in suicide related deaths than natural deaths. In four of the cases benzodiazepines alone were the only cause of death. In Australia, nitrazepam and temazepam were the benzodiazepines most commonly detected in overdose drug related deaths. In a third of cases benzodiazepines were the sole cause of death.
Individuals with chronic illnesses are much more vulnerable to lethal overdose with nitrazepam, as fatal overdoses can occur at relatively low doses in these individuals.
Mogadon, Alodorm, Apodorm, Remnos, Somnite, Apodorm, Arem, Cavodan, Dima, Dormalon, Dormigen, Dormo-Puren, Dumolid, Eatan N, Eunoctin, Hypnotex, Imeson, Insoma, Insomin, Ipersed, Mitidin, Mogadan, Nilandron, Nitavan, Nitepam, Nitrados, Nitrapan, Nitravet, Nitrazadon, Nitrazep, Nitrazepan, Nitrazepol, Nitredon, Nitrosun, Novanox, Numbon, Onirema, Ormodon, Pacisyn, Paxadorm, Pelson, Pelsonfilina, Protraz, Radedorm, Remnos, Serenade, Somnibel N, Somnipar, Somnite, Sonebon, Sonotrat, Surem, Tri, Unisomnia, Nitrazepam Capsules BP 1993, Nitrazepam Oral Suspension BP 1993, Nitrazepam Tablets BP 1993.
In Popular CultureEdit
- Marillion refers to the drug in the song Punch & Judy on their second album Fugazi, with lyricist Fish writing Curling tongs, mogadons, "I got a headache baby, don't take so long"
- Porcupine Tree reference the drug in their song Fear of a Blank Planet from the album of the same name with the line "My face is Mogadon."
- ↑ Yasui M, Kato A, Kanemasa T, Murata S, Nishitomi K, Koike K, Tai N, Shinohara S, Tokomura M, Horiuchi M, Abe K. (Jun 2005). [Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes] 25 (3): 143-51.
- ↑ Rickels K. (1986). The clinical use of hypnotics: indications for use and the need for a variety of hypnotics.. Acta Psychiatr Scand Suppl. 332: 132-41.
- ↑ Robertson MD, Drummer OH. (May 1995). Postmortem drug metabolism by bacteria.. J Forensic Sci. 40 (3): 382-6.
- ↑ Oelschläger H. (4). [Chemical and pharmacologic aspects of benzodiazepines]. Schweiz Rundsch Med Prax. 78 (27-28): 766-72.
- ↑ Podhorna J, Krsiak M. (2000). Behavioural effects of a benzodiazepine receptor partial agonist, Ro 19-8022, in the social conflict test in mice.. Behavioural pharmacology. 11 (2): 143-51.
- ↑ Nowakowska E, Chodera A. (Feb 1991). Studies on the involvement of opioid mechanism in the locomotor effects of benzodiazepines in rats.. Pharmacology, biochemistry, and behavior. 38 (2): 265-6.
- ↑ Tomono S, Kuriyama K. (Dec 1985). Effect of 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative, on cerebral content of neuroactive amino acids.. Jpn J Pharmacol. 39 (4): 558-61.
- ↑ Oishi R, Nishibori M, Itoh Y, Saeki K. (27). Diazepam-induced decrease in histamine turnover in mouse brain.. Eur J Pharmacol. 124 (3): 337-42.
- ↑ Krause L, Shuster S. (22). Mechanism of action of antipruritic drugs.. Br Med J (Clin Res Ed). 287 (6400): 1199-200..
- ↑ Christensen P, Lolk A, Gram LF, Kragh-Sørensen P. (1992). Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers.. Psychopharmacology. 106 (4): 511-6.
- ↑ Earley JV, Fryer RI, Ning RY. (Jul 1979). Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development.. J Pharm Sci. 68 (7): 845-50.
- ↑ Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A. (Apr 2002). Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines.. Biol Pharm Bull. 25 (4): 441-5.
- ↑ Matthew E, Laskin JD, Zimmerman EA, Weinstein IB, Hsu KC, Engelhardt DL (Jun 1981). Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells. Proc Natl Acad Sci U S A 78 (6): 3935-9.
- ↑ Linnoila, M, Viukari M. (Jun 1976). Efficacy and side effects of nitrazepam and thioridazine as sleeping aids in psychogeriatric in-patients.. British Journal of Psychiatry 128: 566-9.
- ↑ Nakazawa Y, Kotorii M, Oshima M, Horikawa S, Tachibana H. (31). Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives.. Psychopharmacologia. 44 (2): 165-71.
- ↑ Adam K, Oswald I. (Jul 1982). A comparison of the effects of chlormezanone and nitrazepam on sleep.. Br J Clin Pharmacol. 14 (1): 57-65.
- ↑ Mizuki Y, Suetsugi M, Hotta H, Ushijima I, Yamada M. (May 1995). Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal humans.. Prog Neuropsychopharmacol Biol Psychiatry. 19 (3): 385-401.
- ↑ Tazaki T, Tada K, Nogami Y, Takemura N, Ishikawa K. (1989). Effects of butoctamide hydrogen succinate and nitrazepam on psychomotor function and EEG in healthy volunteers.. Psychopharmacology (Berl). 97 (3): 370-5.
- ↑ Malpas A, Rowan AJ, Boyce CR, Scott DF. (27). Persistent behavioural and electroencephalographic changes after single doses of nitrazepam and amylobarbitone sodium.. Br Med J. 2 (5712): 762-4.
- ↑ Watanabe S, Ohta H, Sakurai Y, Takao K, Ueki S. (Jul 1986). [Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants]. Nippon Yakurigaku Zasshi. 88 (1): 19-32.
- ↑ Noguchi H, Kitazumi K, Mori M, Shiba T. (Mar 2004). Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats.. J Pharmacol Sci. 94 (3): 246-51.
- ↑ Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C. (Feb 2007). Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats.. J Pharmacol Sci. 103 (2): 201-6.
- ↑ Tokola RA, Neuvonen PJ (1983). Pharmacokinetics of antiepileptic drugs. Acta neurologica Scandinavica. Supplementum 97: 17-27.
- ↑ Hertz MM, Paulson OB. (May 1980). Heterogeneity of cerebral capillary flow in man and its consequences for estimation of blood-brain barrier permeability.. J Clin Invest. 65 (5): 1145-51.
- ↑ Genton D, Kesselring UW. (May 1977). Effect of temperature and relative humidity on nitrazepam stability in solid state.. J Pharm Sci. 66 (5): 676-80.
- ↑ Kangas L, Kanto J, Syvälahti E. (Jul 1977). Plasma nitrazepam concentrations after an acute intake and their correlation to sedation and serum growth hormone levels.. Acta Pharmacol Toxicol (Copenh). 41 (1): 65-73.
- ↑ Kangas L, Kanto J, Siirtola T, Pekkarinen A. (Jul 1977). Cerebrospinal-fluid concentrations of nitrazepam in man.. Acta Pharmacol Toxicol (Copenh). 41 (1): 74-9.
- ↑ Kangas L, Iisalo E, Kanto J, Lehtinen V, Pynnönen S, Ruikka I, Salminen J, Sillanpää M, Syvälahti E. (Apr 1979). Human pharmacokinetics of nitrazepam: effect of age and diseases.. Human pharmacokinetics of nitrazepam: effect of age and diseases. 15 (3): 163-70.
- ↑ Vozeh S. (21). [Pharmacokinetic of benzodiazepines in old age]. Schweiz Med Wochenschr. 111 (47): 1789-93.
- ↑ Holm V, Melander A, Wåhlin-Boll E. (1982). Influence of food and of age on nitrazepam kinetics.. Drug-nutrient interactions. 1 (4): 307-11.
- ↑ Skerritt JH, Johnston GA. (6). Enhancement of GABA binding by benzodiazepines and related anxiolytics.. Eur J Pharmacol. 89 (3-4): 193-8.
- ↑ Sato K, Hong YL, Yang MS, Shibuya T, Kawamoto H, Kitagawa H. (Apr 1985). Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition.. Int J Clin Pharmacol Ther Toxicol. 23 (4): 204-10.
- ↑ McLean MJ, Macdonald RL. (Feb 1988). Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture.. J Pharmacol Exp Ther. 244 (2): 789-95.
- ↑ Date SK, Hemavathi KG, Gulati OD. (Nov 1984). Investigation of the muscle relaxant activity of nitrazepam.. Arch Int Pharmacodyn Ther. 272 (1): 129-39.
- ↑ Farrell K. (1986). Benzodiazepines in the treatment of children with epilepsy.. Epilepsia. 1: 45-5.
- ↑ Munn R, Farrell K. (Nov-Dec 1993). Open study of clobazam in refractory epilepsy.. Pediatr Neurol. 9 (6): 465-9.
- ↑ Isojärvi, JI, Tokola RA. (Dec 1998). Benzodiazepines in the treatment of epilepsy in people with intellectual disability.. J Intellect Disabil Res. 42 (1): 80-92.
- ↑ Djurić M, Marjanović B, Zamurović D. (May-Jun 2001). [West syndrome--new therapeutic approach]. Srp Arh Celok Lek. 129 (1): 72-7.
- ↑ Mant A, Whicker SD, McManus P, Birkett DJ, Edmonds D, Dumbrell D. (Dec 1993). Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database.. Aust J Public Health. 17 (4): 345-9.
- ↑ Jacobson GA, Friesen WT, Peterson GM, Rumble RH, Polack AE. (6). Psychoactive drug prescribing in the Tasmanian community.. Med J Aust. 157 (1): 20-4.
- ↑ Kayed K. (30). [Insomnia and hypnotics]. Tidsskr Nor Laegeforen. 115 (9): 1087-90.
- ↑ Morgan K, Gilleard CJ, Reive A. (Nov 1982). Hypnotic usage in residential homes for the elderly: a prevalence and longitudinal analysis.. Age Ageing. 11 (4): 229-34.
- ↑ Szczawińska K, Cenajek-Musiał D, Nowakowska E, Chodera A. (16). Decrease in [3H]flunitrazepam receptor binding in rats tolerant to the effects of nitrazepam. 147 (1): 7-11.
- ↑ Chodera A, Szczawińska K, Cenajek D, Nowakowska E. (Jul-Aug 1984). Pharmacokinetic aspects of habituation to benzodiazepines.. Pol J Pharmacol Pharm. 36 (4): 353-60.
- ↑ Nowakowska E, Chodera A, Szczawińska K, Cenajek D. (May-Jun 1983). Development of tolerance to benzodiazepines. I. Changes in the systems of central nervous system neurotransmitters during long-term administration of nitrazepam. 34 (3): 345-51.
- ↑ Griffiths AN, Tedeschi G, Richens A. (1986). The effects of repeated doses of temazepam and nitrazepam on several measures of human performance.. Acta psychiatrica Scandinavica. Supplementum. 332: 119-26.
- ↑ Cook PJ, Huggett A, Graham-Pole R, Savage IT, James IM. (8). Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam.. Br Med J (Clin Res Ed). 286 (6359): 100-2..
- ↑ Garratt JC, Gent JP, Feely M, Haigh JR. (5). Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential?. Eur J Pharmacol. 145 (1): 75-80.
- ↑ Loiseau P (1983). [Benzodiazepines in the treatment of epilepsy]. Encephale 9 (4 Suppl 2): 287B-292B.
- ↑ Rooke KC. (1976). The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice.. J Int Med Res. 4 (5): 355-9.
- ↑ MacKinnon GL, Parker WA. (1982). Benzodiazepine withdrawal syndrome: a literature review and evaluation.. The American journal of drug and alcohol abuse. 9 (1): 19-33.
- ↑ Kales A, Scharf MB, Kales JD, Soldatos CR. (20). Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines.. JAMA : the journal of the American Medical Association. 241 (16): 1692-5.
- ↑ Hecker R, Burr M, Newbury G. (1992). Risk of benzodiazepine dependence resulting from hospital admission.. Drug Alcohol Rev. 11 (2): 131-5.
- ↑ Hindmarch I. (Nov 1977). A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.. Acta Psychiatr Scand. 56 (5): 373-81.
- ↑ Viukari M, Linnoila M, Aalto U. (Jan 1978). Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients.. Acta Psychiatr Scand. 57 (1): 27-35.
- ↑ Nowakowska E, Chodera A, Cenajek-Musiał D, Szczawińska K. (May-Jun 1987). Differences in the development of tolerance to various benzodiazepines.. Pol J Pharmacol Pharm. 39 (3): 245-52.
- ↑ Terao T, Tani Y. (1). [Two cases of psychotic state following normal-dose benzodiazepine withdrawal]. J UOEH. 10 (3): 337-40.
- ↑ Tagashira E, Hiramori T, Urano T, Nakao K, Yanaura S. (Oct 1981). Enhancement of drug withdrawal convulsion by combinations of phenobarbital and antipsychotic agents.. Jpn J Pharmacol. 31 (5): 689-99.
- ↑ Terao T, Yoshimura R, Terao M, Abe K. (15). Depersonalization following nitrazepam withdrawal.. Biol Psychiatry. 31 (2): 212-3.
- ↑ Kitabayashi Y, Ueda H, Narumoto J, Iizumi H, Tsuchida H, Murata N, Nakajima S, Fukui K. (Jul 2001). Chronic high-dose nitrazepam dependence 123I-IMP SPECT and EEG studies.. Addict Biol. 6 (3): 257-261.
- ↑ Committee on the Review of Medicines (29). Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines.. Br Med J. 280 (6218): 910-2.
- ↑ Rosen GM, Turner MJ 3rd. (Feb 1988). Synthesis of spin traps specific for hydroxyl radical.. J Med Chem. 31 (2): 428-32.
- ↑ Takeno S, Sakai T. (Aug 1991). Involvement of the intestinal microflora in nitrazepam-induced teratogenicity in rats and its relationship to nitroreduction.. Teratology. 44 (2): 209-14.
- ↑ Rosen GM, Freeman BA. (Dec 1984). Detection of superoxide generated by endothelial cells.. Proc Natl Acad Sci U S A. 81 (23): 7269-73.
- ↑ Mansbach CM 2nd, Rosen GM, Rahn CA, Strauss KE. (29). Detection of free radicals as a consequence of rat intestinal cellular drug metabolism.. Biochim Biophys Acta. 888 (1): 1-9.
- ↑ Rosen GM, Hassett DJ, Yankaskas JR, Cohen MS. (Jun 1989). Detection of free radicals as a consequence of dog tracheal epithelial cellular xenobiotic metabolism.. Xenobiotica. 19 (6): 635-43.
- ↑ Kersten B, Kasper P, Brendler-Schwaab SY, Müller L. (26). Use of the photo-micronucleus assay in Chinese hamster V79 cells to study photochemical genotoxicity.. Mutation Research. 519 (1-2): 49-66.
- ↑ Giri AK, Banerjee S. (Jun 1996). Genetic toxicology of four commonly used benzodiazepines: a review.. Mutation Research. 340 (2-3): 93-108.
- ↑ Ban Y, Naya M, Nishimura T, Kaneto M, Kishi K, Inoue T, Yoshizaki H, Ooshima Y. (Feb 2001). Collaborative study on rat sperm motion analysis using CellSoft Series 4000 semen analyzer.. J Toxicol Sci. 26 (1): 9-24.
- ↑ Kishi K, Kanamori S, Maruyama T, Sasaki K, Hara K, Kawai M, Ikeuchi K. (Aug 1995). Potential parameters of male reproductive toxicity: reproductive performance, histopathology and sperm evaluation in SD rats given nitrazepam.. J Toxicol Sci. 20 (3): 329-39.
- ↑ Kaneto M, Kanamori S, Hara K, Kishi K. (1999). Characterization of epididymal sperm motion and its correlation with stages of target cells in rats given alpha-chlorohydrin, cyclophosphamide or nitrazepam.. The Journal of toxicological sciences. 24 (3): 187-97.
- ↑ Sanbuissho A, Terada S, Suzuki K, Masuda N, Teranishi M, Masuda H. (Aug 1995). Male reproductive toxicity study of nitrazepam in rats.. J Toxicol Sci. 20 (3): 319-28.
- ↑ Kar RN, Das RK. (1983). Induction of sperm head abnormalities in mice by three tranquilizers.. Cytobios. 36 (141): 45-51.
- ↑ Garretty DJ, Wolff K, Hay AW, Raistrick D. (Jan 1997). Benzodiazepine misuse by drug addicts.. Annals of clinical biochemistry. 34 (Pt 1): 68-73.
- ↑ Saito H, Kobayashi H, Takeno S, Sakai T. (1984). Fetal toxicity of benzodiazepines in rats.. Res Commun Chem Pathol Pharmacol. 46 (3): 437-47.
- ↑ Takeno S, Hirano Y, Kitamura A, Sakai T. (Aug 1993). Comparative developmental toxicity and metabolism of nitrazepam in rats and mice.. Toxicol Appl Pharmacol. 121 (2): 233-8.
- ↑ Takeno S, Nakagawa M, Sakai T. (Jul 1990). Teratogenic effects of nitrazepam in rats.. Res Commun Chem Pathol Pharmacol. 69 (1): 59-70.
- ↑ Saito H, Kobayashi H, Takeno S, Sakai T, Ishii H. (Jun 1986). In vivo and in vitro studies on fetal toxicity of benzodiazepines in rats.. Res Commun Chem Pathol Pharmacol. 52 (3): 295-304.
- ↑ Rintahaka PJ, Nakagawa JA, Shewmon DA, Kyyronen P, Shields WD. (Apr 1999). Incidence of death in patients with intractable epilepsy during nitrazepam treatment.. Epilepsia. 40 (4): 492-6.
- ↑ Lim HC, Nigro MA, Beierwaltes P, Tolia V, Wishnow R. (Sep 1992). Nitrazepam-induced cricopharyngeal dysphagia, abnormal esophageal peristalsis and associated bronchospasm: probable cause of nitrazepam-related sudden death. 14 (5): 309-14.
- ↑ Professor C Heather Ashton (2002). BENZODIAZEPINE ABUSE. Drugs and Dependence. Harwood Academic Publishers.
- ↑ Garretty DJ, Wolff K, Hay AW, Raistrick D. (Jan 1997). Benzodiazepine misuse by drug addicts.. Annals of clinical biochemistry. 34 (Pt 1): 68-73.
- ↑ Chatterjee A, Uprety L, Chapagain M, Kafle K. (1996). Drug abuse in Nepal: a rapid assessment study.. Bull Narc. 48 (1-2): 11-33..
- ↑ Thiébot MH, Le Bihan C, Soubrié P, Simon P. (1985). Benzodiazepines reduce the tolerance to reward delay in rats.. Psychopharmacology (Berl). 86 (1-2): 147-52.
- ↑ Bergman U, Dahl-Puustinen ML. (1989). Use of prescription forgeries in a drug abuse surveillance network.. Eur J Clin Pharmacol. 36 (6): 621-3.
- ↑ Jones AW, Holmgren A, Kugelberg FC. (Apr 2007). Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results.. Ther Drug Monit. 29 (2): 248-60.
- ↑ Cosbey SH. (Dec 1986). Drugs and the impaired driver in Northern Ireland: an analytical survey.. Forensic Sci Int. 32 (4): 245-58.
- ↑ Morgan K, Dixon S, Mathers N, Thompson J, Tomeny M. (Feb 2004). Psychological treatment for insomnia in the regulation of long-term hypnotic drug use.. Health Technol Assess. 8 (8): 1-68.
- ↑ Sanders LD, Yeomans WA, Rees J, Rosen M, Robinson JO. (Nov 1988). A double-blind comparison between nitrazepam, lorazepam, lormetazepam and placebo as preoperative night sedatives.. Eur J Anaesthesiol. 5 (6): 377-83.
- ↑ Liljequist R, Mattila MJ. (May 1979). Acute effects of temazepam and nitrazepam on psychomotor skills and memory.. Acta Pharmacol Toxicol (Copenh). 44 (5): 364-9.
- ↑ Nabeshima T, Tohyama K, Ichihara K, Kameyama T. (Nov 1990). Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and the cholinergic neuronal system.. J Pharmacol Exp Ther. 255 (2): 789-94.
- ↑ Antkiewicz-Michaluk, L, Grabowska M, Baran L, Michaluk J. (1975). Influence of benzodiazepines on turnover of serotonin in cerebral structures in normal and aggressive rats.. Arch Immunol Ther Exp (Warsz). 23(6): 763-7.
- ↑ Vermeeren A. (2004). Residual effects of hypnotics: epidemiology and clinical implications.. CNS Drugs. 18 (5): 297-328.
- ↑ Richens A, Mercer AJ, Jones DM, Griffiths A, Marshall RW. (Jul 1993). Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo controlled study in healthy volunteers.. British journal of clinical pharmacology. 36 (1): 61-5.
- ↑ Morgan K. (1985). Effects of repeated dose nitrazepam and lormetazepam on psychomotor performance in the elderly.. Psychopharmacology (Berl). 86 (1-2): 209-11.
- ↑ Morgan K. (1984). Effects of two benzodiazepines on the speed and accuracy of perceptual-motor performance in the elderly.. Psychopharmacology Suppl. 1: 79-83.
- ↑ 97.0 97.1 Hossmann V, Maling TJ, Hamilton CA, Reid JL, Dollery CT. (Aug 1980). Sedative and cardiovascular effects of clonidine and nitrazepam.. Clin Pharmacol Ther. 28 (2): 167-76.
- ↑ Impallomeni M, Ezzat R. (24). Letter: Hypothermia associated with nitrazepam administration.. Br Med J. 1 (6003): 223-4.
- ↑ MacLean H. (24). Nitrazepam: another interesting syndrome.. Br Med J. 1 (5851): 488.
- ↑ Luurila H, Olkkola KT, Neuvonen PJ. (Apr 1995). Interaction between erythromycin and nitrazepam in healthy volunteers.. Pharmacol Toxicol. 76 (4): 255-8.
- ↑ Tokinaga N, Kondo T, Kaneko S, Otani K, Mihara K, Morita S. (Dec 1996). Hallucinations after a therapeutic dose of benzodiazepine hypnotics with co-administration of erythromycin. 50 (6): 337-9.
- ↑ Back DJ, Orme ML. (Jun 1990). Pharmacokinetic drug interactions with oral contraceptives.. Clin Pharmacokinet. 18 (6): 472-84.
- ↑ Brockmeyer NH, Mertins L, Klimek K, Goos M, Ohnhaus EE. (Sep 1990). Comparative effects of rifampin and/or probenecid on the pharmacokinetics of temazepam and nitrazepam.. Int J Clin Pharmacol Ther Toxicol. 28 (9): 387-93.
- ↑ Ochs HR, Greenblatt DJ, Gugler R, Müntefering G, Locniskar A, Abernethy DR. (Aug 1983). Cimetidine impairs nitrazepam clearance.. Clin Pharmacol Ther. 34 (2): 227-30.
- ↑ Zácková P, Kvĕtina J, Nĕmec J, Nĕmcová J. (Dec 1982). Cardiovascular effects of diazepam and nitrazepam in combination with ethanol.. Pharmazie. 37 (12): 853-6.
- ↑ Pacifici GM, Gustafsson LL, Säwe J, Rane A. (Apr 1986). Metabolic interaction between morphine and various benzodiazepines.. Acta Pharmacol Toxicol (Copenh). 58 (4): 249-52.
- ↑ Lahtinen U, Lahtinen A, Pekkola P. (Feb 1978). The effect of nitrazepam on manual skill, grip strength, and reaction time with special reference to subjective evaluation of effects on sleep.. Acta Pharmacol Toxicol (Copenh). 42 (2): 130-4.
- ↑ Kozená L, Frantik E, Horváth M. (May 1995). Vigilance impairment after a single dose of benzodiazepines.. Psychopharmacology (Berl). 119 (1): 39-45.
- ↑ Törnros J, Laurell H. (Jul 1990). Acute and carry-over effects of brotizolam compared to nitrazepam and placebo in monotonous simulated driving.. Pharmacol Toxicol. 67 (1): 77-80.
- ↑ Hindmarch I, Parrott AC. (1980). The effects of combined sedative and anxiolytic preparations on subjective aspects of sleep and objective measures of arousal and performance the morning following nocturnal medication. I: Acute doses.. Arzneimittelforschung. 30 (6): 1025-8.
- ↑ Shats V, Kozacov S. (1). [Falls in the geriatric department: responsibility of the care-giver and the hospital]. Harefuah 128 (11): 690-3.
- ↑ Borland RG, Nicholson AN. (Feb 1975). Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.. Br J Clin Pharmacol. 2 (1): 9-17.
- ↑ Evans JG, Jarvis EH. (25). Nitrazepam and the elderly.. Br Med J. 4 (5838): 487.
- ↑ Trewin VF, Lawrence CJ, Veitch GB. (Apr 1992). An investigation of the association of benzodiazepines and other hypnotics with the incidence of falls in the elderly.. J Clin Pharm Ther. 17 (2): 129-33.
- ↑ Greenblatt DJ, Allen MD. (May 1978). Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.. British journal of clinical pharmacology. 5 (5): 407-13.
- ↑ Castleden CM, George CF, Marcer D, Hallett C. (1). Increased sensitivity to nitrazepam in old age.. Br Med J. 1 (6052): 10-2.
- ↑ Figols J, Cervós-Navarro J, Wolman M. (Jan 1986). Encephalopathy with astrocytic residual bodies. Report of a case and review of the literature.. Histol Histopathol. 1 (1): 59-67.
- ↑ Dennis J, Hunt A. (14). Prolonged use of nitrazepam for epilepsy in children with tuberous sclerosis.. Br Med J (Clin Res Ed). 291 (6497): 692-3.
- ↑ Kenny RA, Kafetz K, Cox M, Timmers J, Impallomeni M. (Apr 1984). Impaired nitrazepam metabolism in hypothyroidism.. Postgrad Med J. 60 (702): 296-7.
- ↑ Olive G, Dreux C. (Jan 1977). Pharmacologic bases of use of benzodiazepines in peréinatal medicine.. Arch Fr Pediatr. 34 (1): 74-89..
- ↑ Kangas L, Kanto J, Erkkola R. (16). Transfer of nitrazepam across the human placenta.. Eur J Clin Pharmacol. 12 (5): 355-7.
- ↑ Kanto JH. (May 1982). Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations.. Drugs. 23 (5): 354-80.
- ↑ McElhatton PR. (Nov-Dec 1994). The effects of benzodiazepine use during pregnancy and lactation.. Reprod Toxicol. 8 (6): 461-75.
- ↑ Midgren B, Hansson L, Ahlmann S, Elmqvist D. (1990). Effects of single doses of propiomazine, a phenothiazine hypnotic, on sleep and oxygenation in patients with stable chronic obstructive pulmonary disease.. Respiration. 57 (4): 239-42.
- ↑ O'Hanlon JF, Volkerts ER. (1986). Hypnotics and actual driving performance.. Acta Psychiatr Scand Suppl. 332: 95-104.
- ↑ Zevzikovas A, Kiliuviene G, Ivanauskas L, Dirse V. (2002). [Analysis of benzodiazepine derivative mixture by gas-liquid chromatography]. Medicina (Kaunas). 38 (3): 316-20.
- ↑ Lai SH, Yao YJ, Lo DS. (Oct 2006). A survey of buprenorphine related deaths in Singapore.. Forensic Sci Int. 162 (1-3): 80-6.
- ↑ Rumpl E, Prugger M, Battista HJ, Badry F, Gerstenbrand F, Dienstl F. (Dec 1988). Short latency somatosensory evoked potentials and brain-stem auditory evoked potentials in coma due to CNS depressant drug poisoning. Preliminary observations. 70 (6): 482-9.
- ↑ Carlsten, A, Waern M, Holmgren P, Allebeck P. (2003). The role of benzodiazepines in elderly suicides.. Scand J Public Health. 31 (3): 224-8.
- ↑ Moriya F, Hashimoto Y. (28). Tissue distribution of nitrazepam and 7-aminonitrazepam in a case of nitrazepam intoxication.. Forensic Sci Int. 131 (2-3): 108-12.
- ↑ Ericsson HR, Holmgren P, Jakobsson SW, Lafolie P, De Rees B. (10). [Benzodiazepine findings in autopsy material. A study shows interacting factors in fatal cases]. Läkartidningen. 90 (45): 3954-7.
- ↑ Drummer OH, Ranson DL. (Dec 1996). Sudden death and benzodiazepines.. Am J Forensic Med Pathol. 17 (4): 336-42.
- ↑ Brødsgaard I, Hansen AC, Vesterby A. (Jun 1995). Two cases of lethal nitrazepam poisoning.. Am J Forensic Med Pathol. 16 (2): 151-3.
- Adams, R. G. (1974). Pre-sleep ingestion of two hypnotic drugs and subsequent performance: Psychopharmacologia Vol 40(2) 1974, 185-190.
- Al Nasheet, F., Al-Haddad, M. K., & Mathur, V. S. (1994). Routine use of hypnotics in a psychiatric hospital: Arab Journal of Psychiatry Vol 5(1) May 1994, 57-58.
- Aleksandrovskii, Y. A. (1970). On the main criteria for clinical assessment of tranquilizer action: Zhurnal Nevropatologii i Psikhiatrii Vol 70(12) Dec 1970, 1873-1882.
- Andersen, T., & Lingjaerde, O. (1969). Nitrazepam (mogadon) as a sleep-inducing agent: British Journal of Psychiatry 115(529) 1969, 1393-1397.
- Anon. (1970). Sleeping pills: BMJ: British Medical Journal Vol 3(5718) Aug 1970, 296-297.
- Ashton, H., Millman, J. E., Telford, R., & Thompson, J. W. (1974). The effect of caffeine, nitrazepam and cigarette smoking on the contingent negative variation in man: Electroencephalography & Clinical Neurophysiology Vol 37(1) Jul 1974, 59-71.
- Ballinger, B. R., Presly, A., Reid, A. H., & Stevenson, I. H. (1974). The effects of hypnotics on imipramine treatment: Psychopharmacologia Vol 39(3) 1974, 267-274.
- Banerjee, U. (1974). Programmed self-administration of potentially addictive drugs in young rats and its effects on learning: Psychopharmacologia Vol 38(2) 1974, 111-124.
- Bathien, N., Ferreri, M., & Alby, J. M. (1980). Fluctuations in the psychophysiological responses to activation in depressive states: Annales Medico-Psychologiques Vol 138(8) Sep-Oct 1980, 974-985.
- Beyer, K. H., & Sadee, W. (1969). Spectrophotometric determination of 5-phenyl-1, 4-benzodiazepine derivatives and investigations on the metabolism of nitrazepam: Arzneimittel-Forschung Vol 19(12) Dec 1969, 1929-1931.
- Blumenthal, M., Byring, R., & Koivula, K. (1980). Comparison of nitrazepam 5 mg with triazolam 0.5 mg in young psychiatric insomniac inpatients: Double-blind single night cross-over study: Acta Psychiatrica Scandinavica Vol 62(5) Nov 1980, 519-524.
- Bond, A. J., & Lader, M. H. (1972). Residual effects of hypnotics: Psychopharmacologia Vol 25(2) 1972, 117-132.
- Bongenaar, T. C., & et al. (1985). Results of a multicentre, double-blind study under general practice conditions with the new hypnotic, lormetazepam: Current Therapeutic Research Vol 38(2) Aug 1985, 204-214.
- Bordeleau, J. M., Charland, P., & Tetreault, L. (1970). Hypnotic properties of nitrazepam (mogadon): A comparative study of chlordiazepoxide, diazepam, nitrazepam, secobarbital and placebo in psychiatric patients: Diseases of the Nervous System Vol 31(5) May 1970, 318-323.
- Borenstein, P., & et al. (1973). Behavioral and polygraphic study of 3 benzodiazepines and a barbiturate in the freely moving cat with implanted electrodes: Annales Medico-Psychologiques Vol 2(1) Jun 1973, 13-43.
- Borenstein, P., Soret, C., & Cujo, P. (1973). Influence of 3 benzodiazepines and a barbiturate on the electroencephalogram of night-sleep in man: Annales Medico-Psychologiques Vol 2(1) Jun 1973, 1-12.
- Borsini, F., Lecci, A., Volterra, G., & Meli, A. (1989). A model to measure anticipatory anxiety in mice? : Psychopharmacology Vol 98(2) Jun 1989, 207-211.
- Bourin, M., Hubert, C., Colombel, M. C., & Larousse, C. (1987). Residual effects of temazepam versus nitrazepam on memory and vigilance in the normal subject: Human Psychopharmacology: Clinical and Experimental Vol 2(3) Sep 1987, 185-189.
- Broekkamp, C. L., Le Pichon, M., & Lloyd, K. G. (1984). The comparative effects of benzodiazepines, progabide and PK 9084 on acquisition of passive avoidance in mice: Psychopharmacology Vol 83(1) 1984, 122-125.
- Capovilla, G., Beccaria, F., Montagnini, A., Cusmai, R., Franzoni, E., Moscano, F., et al. (2003). Short-term Nonhormonal and Nonsteroid Treatment in West Syndrome: Epilepsia Vol 44(8) Aug 2003, 1085-1088.
- Chamberlain, M. C. (1996). Nitrazepam for refractory infantile spasm and the Lennox-Gastaut syndrome: Journal of Child Neurology Vol 11(1) Jan 1996, 31-34.
- Chang-An, C., & Jian-Jun, Z. (2006). A Controlled Study of Mirtazapine and Nitrazepam in the Treatment of Insomnia and Anxiety of Heroin Addicts after Detoxification: Chinese Mental Health Journal Vol 20(6) Jun 2006, 416-417, 419.
- Christensen, P., Lolk, A., Gram, L. F., & Kragh-Sorensen, P. (1992). Benzodiazepine-induced sedation and cortisol suppression: A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers: Psychopharmacology Vol 106(4) Apr 1992, 511-516.
- Christmas, A. J., & Maxwell, D. R. (1970). A comparison of the effects of some benzodiazepines and other drugs on aggressive and exploratory behaviour in mice and rats: Neuropharmacology 9(1) 1970, 17-29.
- Chweh, A. Y., Yung Bor, L., & Swinyard, E. A. (1984). Hypnotic action of benzodiazepines: A possible mechanism: Life Sciences Vol 34(18) Apr 1984, 1763-1768.
- Collard, J. (1969). Nitrazepam, an anxiolytique derived from chlordiazepoxide (librium), and its place in the spectre of psychorelaxants diazepiniques: Acta Neurologica et Psychiatrica Belgica Vol 69(12) Dec 1969, 1038-1047.
- Collard, J. (1971). Initial psychopharmacological study of lorazepam (Wy 4036): Arzneimittel-Forschung Vol 21(7a) Jul 1971, 1091-1095.
- Collard, J. (1972). Control of insomnia with a new benzodiazepine: The flunidazepam or Ro 5-4200 (first investigation of phase I and controlled investigation of phase II): Acta Psychiatrica Belgica Vol 72(6) Nov 1972, 721-735.
- Cook, P. J. (1986). Benzodiazepine hypnotics in the elderly: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 149-158.
- Corrodi, H., Fuxe, K., Lidbrink, P., & Olson, L. (1971). Minor tranquillizers, stress and central catecholamine neurons: Brain Research Vol 29(1) 1971, 1-16.
- Cruz, A. P. M., Frei, F., & Graeff, F. G. (1994). Ethopharmacological analysis of rat behavior on the elevated plus-maze: Pharmacology, Biochemistry and Behavior Vol 49(1) Sep 1994, 171-176.
- Dahl, L. E., Dencker, S. J., Lundin, L., & Kullingsjo, H. (1982). Comparison of nitrazepam with triazolam in insomniac outpatients: Acta Psychiatrica Scandinavica Vol 65(2) Feb 1982, 86-92.
- David, J., Grewal, R. S., & Wagle, G. P. (1974). Persistent electroencephalographic changes in rhesus monkeys after single doses of pentobarbital, nitrazepam and imipramine: Psychopharmacologia Vol 35(1) 1974, 61-75.
- Davies, C., & Levine, S. (1967). A Controlled Comparison of Nitrazepam ("Mogadon") with Sodium Amylobarbitone as a Sleep-Inducing Agent: British Journal of Psychiatry 113(502) 1967, 1005-1008.
- DeClerk, A. C., & Bisserbe, J. C. (1997). Short-term safety profile of zolpidem: Objective measures of cognitive effects: European Psychiatry Vol 12(1) 1997, 15s-20s.
- Dehlin, O., & Bjornson, G. (1983). Triazolam as a hypnotic for geriatric patients: A double-blind cross-over comparison of nitrazepam and triazolam regarding effects on sleep and psychomotor performance: Acta Psychiatrica Scandinavica Vol 67(5) May 1983, 290-296.
- Douglas, R. J., & Scott, D. W. (1972). The differential effects of nitrazepam on certain inhibitory and excitatory behaviors: Psychonomic Science Vol 26(3) Feb 1972, 164-166.
- Dundar, Y., Dodd, S., Strobl, J., Boland, A., Dickson, R., & Walley, T. (2004). Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: A systematic review and meta-analysis: Human Psychopharmacology: Clinical and Experimental Vol 19(5) Jul 2004, 305-322.
- Dzhagatspanyan, I. A., Klygul, T. A., & Vikhlyaev, Y. I. (1972). Distinctive features peculiar to the development of tolerance for tranquilizers of the benzodiazepine series measured by the muscle relaxant and sedative effects: Farmakologiya i Toksikologiya Vol 35(4) Jul 1972, 421-425.
- Ellingsen, A. (1983). Double-blind trial of triazolam 0.5 mg vs. nitrazepam 5 mg in outpatients: Acta Psychiatrica Scandinavica Vol 67(3) Mar 1983, 154-158.
- Etzler, K., & et al. (1969). Study on the statistical interactions between ethylalcohol and carbamazepine, methaqualone, and nitrazepam: Arzneimittel-Forschung Vol 19(6) Jun 1969, 988-995.
- Fenelon, B., & Wortley, S. (1973). Effect of auxiliary acoustic stimulation on two-flash fusion thresholds of reading disabled children: A study using nitrazepam: Perceptual and Motor Skills Vol 36(2) Apr 1973, 443-450.
- Ferrara, N., & et al. (1985). Comparison between brotizolam and nitrazepam in geriatric patients: Randomized and cross-over double-blind clinical study: Current Therapeutic Research Vol 37(2) Feb 1985, 295-308.
- Firth, H. (1974). Sleeping pills and dream content: British Journal of Psychiatry Vol 124 Jun 1974, 547-553.
- Firth, H., & Oswald, I. (1975). Eye movements and visually active dreams: Psychophysiology Vol 12(5) Sep 1975, 602-606.
- Fisenko, V. P., & Machula, A. I. (1979). The effect of tranquilizers on brain cortex excitability in cats: Farmakologiya i Toksikologiya Vol 42(1) Jan-Feb 1979, 15-19.
- Fossen, A., Godlibsen, O. B., Loyning, Y., & Dreyfus, J. F. (1982). Effects of hypnotics on memory: International Pharmacopsychiatry Vol 17(Suppl 2) 1982, 116-126.
- Gardner, C. R. (1989). Discriminative stimulus properties of CL218872 and chlordiazepoxide in the rat: Pharmacology, Biochemistry and Behavior Vol 34(4) Dec 1989, 711-715.
- Goswami, U., & Ray, R. (1985). Anti-arrhythmic potential of doxepin: A case report: Indian Journal of Psychological Medicine Vol 8(2) Jul 1985, 57-59.
- Greenblatt, D. J., & Shader, R. I. (1991). Benzodiazepines in the elderly: Pharmacokinetics and drug sensitivity. New York, NY: Springer Publishing Co.
- Griffiths, A. N., Tedeschi, G., & Richens, A. (1986). The effects of repeated doses of temazepam and nitrazepam on several measures of human performance: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 119-126.
- Grundstrom, R., Holmberg, G., & Hansen, T. (1978). Degree of sedation obtained with various doses of diazepam and nitrazepam: Acta Pharmacologica et Toxicologica Vol 43(1) Jul 1978, 13-18.
- Guy, A. P., & Gardner, C. R. (1985). Pharmacological characterisation of a modified social interaction model of anxiety in the rat: Neuropsychobiology Vol 13(4) Sep 1985, 194-200.
- Haider, I. (1968). A Double-Blind Controlled Trial of a Non-Barbiturate Hypnotic: Nitrazepam: British Journal of Psychiatry 114(508) 1968, 337-343.
- Haider, I., Matthew, H., & Oswald, I. (1971). Electroencephalographic changes in acute drug poisoning: Electroencephalography & Clinical Neurophysiology Vol 30(1) Jan 1971, 23-31.
- Haider, I., & Oswald, I. (1971). Effects of amylobarbitone and nitrazepam on the electrodermogram and other features of sleep: British Journal of Psychiatry Vol 118(546) May 1971, 519-522.
- Harenko, A. (1985). Insomnia in the elderly: Psychiatria Fennica Suppl 1985, 181-188.
- Hartelius, H., & et al. (1978). A controlled long-term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects: Acta Psychiatrica Scandinavica Vol 58(1) Jul 1978, 1-15.
- Hatayama, T., Yamaguchi, H., & Ohyama, M. (1984). Acute behavioral effects of a single dosage of temazepam and nitrazepam on reactive skills: Japanese Psychological Research Vol 26(4) 1984, 201-209.
- Hecker, R., Burr, M., & Newbury, G. (1992). Risk of benzodiazepine dependence resulting from hospital admission: Drug and Alcohol Review Vol 11(2) 1992, 131-135.
- Hesso, R., Retterstol, N., & Torp, H. (1975). Clinical trial with a new substance (PLP 100-127) in order to assess therapeutic efficacy and dependence creating properties: Behavioral Neuropsychiatry Vol 7(1-12) Apr-Dec 1975-1976, 13-17.
- Hicks, R., & et al. (1981). The pharmacokinetics of psychotropic medication in the elderly: A review: Journal of Clinical Psychiatry Vol 42(10) Oct 1981, 374-385.
- Hindmarch, I. (1977). A repeated dose comparison of three benzodiazepine derivatives (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication: Acta Psychiatrica Scandinavica Vol 56(5) Nov 1977, 373-381.
- Hindmarch, I. (1986). Psychopharmacological aspects of idiopathic and transient insomnia: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 47-54.
- Hindmarch, I. (1990). Immediate and overnight effects of zopiclone 7.5 mg and nitrazepam 5 mg with ethanol, on psychomotor performance and memory in healthy volunteers: International Clinical Psychopharmacology Vol 5(Suppl 2) Apr 1990, 105-113.
- Hindmarch, I. (1991). Residual effects of hypnotics: An update: Journal of Clinical Psychiatry Vol 52(Suppl) Jul 1991, 14-15.
- Hoffmeister, F. (1972). Electroencephalogram and behavior of rabbits in physiological and drug-induced sleep: II. EEG of the rabbit in drug-induced sleep: Arzneimittel-Forschung Vol 22(2) Feb 1972, 412-421.
- Hoffmeister, F. (1972). Electroencephalogram and behavior of rabbits in physiological and drug-induced sleep: III. Influence of hypnotics on sleep behavior of rabbits: Discussion and summary: Arzneimittel-Forschung Vol 22(3) Mar 1972, 563-569.
- Hussaini, I. M., & Musa, M. H. (1994). Fluoxetine potentiates nitrazepam-induced behavioral sleep in young chicks: Physiology & Behavior Vol 55(2) Feb 1994, 391-393.
- Inanaga, K., Tanaka, M., & Mizuki, Y. (1982). Prediction of clinical efficacy of zopiclone by utilizing two psychophysiological tools in healthy volunteers: International Pharmacopsychiatry Vol 17(Suppl 2) 1982, 109-115.
- Isojarvi, J. I., & Tokola, R. A. (1998). Benzodiazepines in the treatment of epilepsy in people with intellectual disability: Journal of Intellectual Disability Research Vol 42(Suppl 1) Dec 1998, 80-92.
- Isozaki, H., Tanaka, M., & Inanaga, K. (1976). Effect of a triazolobenzodiazepine derivative, estazolam, on all-night sleep pattern: Current Therapeutic Research Vol 20(4, Pt 2) Oct 1976, 493-509.
- Jain, R. (2000). Utility of thin layer chromatography for detection of opioids and benzodiazepines in a clinical setting: Addictive Behaviors Vol 25(3) May-Jun 2000, 451-454.
- Jochemsen, R., & Breimer, D. D. (1986). Pharmacokinetics of temazepam compared with other benzodiazepine hypnotics: Some clinical consequences: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 20-31.
- Joseph, M. H., & et al. (1985). MHPG excretion in endogenous depression: Relationship to clinical state and the effects of ECT: Psychopharmacology Vol 87(4) Dec 1985, 442-448.
- Jovanovic, U. J., & Dreyfus, J. F. (1982). Polygraphical sleep recordings in insomniac patients under zopiclone or nitrazepam: International Pharmacopsychiatry Vol 17(Suppl 2) 1982, 136-145.
- Julou, L., & et al. (1982). Pharmacological studies on Zopiclone: International Pharmacopsychiatry Vol 17(Suppl 2) 1982, 46-58.
- Kangas, L., Kanto, J., Lehtinen, V., & Salminen, J. (1979). Long-term nitrazepam treatment in psychiatric out-patients with insomnia: Psychopharmacology Vol 63(1) 1979, 63-66.
- Kanto, J. (1985). The pharmacokinetic aspects of benzodiazepines in choosing the drug for insomnia: Psychiatria Fennica Suppl 1985, 189-207.
- Kiseleva, O. V. (1979). Effect of tranquilizers on interaction of the systems of positive and negative reinforcement: Farmakologiya i Toksikologiya Vol 42(4) 1979, 346-348.
- Kleinlogel, H. (1985). Spontaneous EEG paroxysms in the rat: Effects of psychotropic and alpha-adrenergic agents: Neuropsychobiology Vol 13(4) Sep 1985, 206-213.
- Klygul, T. A. (1976). Features peculiar to the development of tolerance for nitrazepam (neozepam) and phenobarbital (luminal) under experimental conditions: Farmakologiya i Toksikologiya Vol 39(5) 1976, 532-537.
- Kozena, L., Frantik, E., & Horvath, M. (1995). Vigilance impairment after a single dose of benzodiazepines: Psychopharmacology Vol 119(1) May 1995, 39-46.
- Kozena, L., Frantik, E., & Horvath, M. (1997). Pharmacologically induced decrease in vigilance measured by two different psychological methods: Homeostasis in Health and Disease Vol 38(2) 1997, 64-65.
- Kozlovskaya, M. M., Mekhedova, A. Y., & Nikuradze, V. O. (1989). Modulating impact of psychotropic drugs on emotional-motivational components of goal-oriented behavioral acts. Amsterdam, Netherlands: Gordon and Breach Publishers.
- Krsiak, M., & Sulcova, A. (1990). Differential effects of six structurally related benzodiazepines on some ethological measures of timidity, aggression and locomotion in mice: Psychopharmacology Vol 101(3) Jul 1990, 396-402.
- Kudo, Y. (1982). Hypnotic effects of a benzodiazepine derivative: A clinical observation: International Pharmacopsychiatry Vol 17(1) 1982, 49-64.
- Kullander, N. E. (1969). A double-blind clinical trial of a new sleep-inducing combination of methaqualone and etodroxizine compared with nitrazepam and placebo: Arzneimittel-Forschung Vol 19(9) Sep 1969, 1530-1532.
- Lahtinen, U., Lahtinen, A., & Pekkola, P. (1978). The effect of nitrazepam on manual skill, grip strength, and reaction time with special reference to subjective evaluation of effects on sleep: Acta Pharmacologica et Toxicologica Vol 42(2) Feb 1978, 130-134.
- Lanoir, J., & Killam, E. K. (1968). Alteration in the sleep-wakefulness patterns by benzodiazepines in the cat: Electroencephalography & Clinical Neurophysiology 25(6) 1968, 530-542.
- Lemperiere, T., & et al. (1980). Study of vigilance after ingestion of zopiclone in comparison with nitrazepam and placebo. Methodology: Self-rating questionnaires and psychometric tests: L'Encephale Vol 6(1) 1980, 23-35.
- Leucuta, S. E., Pop, R. D., & Fodoreanu, L. (1983). Pharmacokinetics of benzodiazepines manufactured in Romania and their importance for therapy: Revista de Medicina Interna, Neurologie, Psihiatrie, Neurochirurgie, Dermato-Venerologie Vol 28(2) Apr-Jun 1983, 131-138.
- Lienert, G. A., Kohnen, R., & Keuchel, I. (1982). Need for hypnotics in young and elderly healthy subjects: Zeitschrift fur Gerontologie Vol 15(1) Jan-Feb 1982, 50-52.
- Lingjaerde, O., & et al. (1978). Alimemazine (trimeprazine, vallergan) as a hypnotic in general practice patients: A controlled comparison with nitrazepam: Current Therapeutic Research Vol 24(4) Aug 1978, 388-396.
- Linnoila, M., & Viukari, M. (1976). Efficacy and side effects of nitrazepam and thioridazine as sleeping aids in psychogeriatric in-patients: British Journal of Psychiatry Vol 128 Jun 1976, 566-569.
- Lison, M. P. (1969). Myoclonic seizures: A comparative study of the anticonvulsant potency of nitrazepam (Mogadon) and diazepam (Valium): Arquivos de Neuro-Psiquiatria Vol 27(3) Sep 1969, 189-198.
- Lison, M. P. (1970). Axo-tonic seizures and akinetic seizures: Clinical study of patients treated by benzodiazepines: Arquivos de Neuro-Psiquiatria Vol 28(4) Dec 1970, 347-356.
- Lison, M. P. (1970). Massive spasms: Clinical study in patients treated by nitrazepam (mogadon): Arquivos de Neuro-Psiquiatria Vol 28(4) Dec 1970, 336-346.
- MacKinnon, G. L., & Parker, W. A. (1982). Benzodiazepine withdrawal syndrome: A literature review and evaluation: American Journal of Drug and Alcohol Abuse Vol 9(1) 1982, 19-33.
- Maldonado, R., Mico, J. A., Valverde, O., Saavedra, M. C., & et al. (1991). Influence of different benzodiazepines on the experimental morphine abstinence syndrome: Psychopharmacology Vol 105(2) Oct 1991, 197-203.
- Malpas, A. (1972). Subjective and objective effects of nitrazepam and amylobarbitone sodium in normal human beings: Psychopharmacologia Vol 27(4) 1972, 373-378.
- Malpas, A., & Joyce, C. R. (1969). Effects of nitrazepam, amylobarbitone and placebo on some perceptual, motor and cognitive tasks in normal subjects: Psychopharmacologia 14(3) 1969, 167-177.
- Marriott, P. (1976). Mandies are not dandy: Another adverse drug interaction with methaqualone: Comprehensive Psychiatry Vol 17(6) Nov-Dec 1976, 779-780.
- Matejcek, M., Neff, G., Abt, K., & Wehrli, W. (1983). Pharmaco-EEG and psychometric study of the effect of single doses of temazepam and nitrazepam: Neuropsychobiology Vol 9(1) Jan-Feb 1983, 52-65.
- Mattila, M. J., Aranko, K., Mattila, M. E., & Stromberg, C. (1985). Objective and subjective assessment of hangover during subacute administration of temazepam and nitrazepam to healthy subjects: Psychiatria Fennica Suppl 1985, 211-221.
- Mellerup, E. T., Dam, H., Lauritzen, L., & Plenge, P. (1991). Platelet -3H-imipramine and -3H-paroxetine binding during treatment with psychoactive drugs: Biological Psychiatry Vol 30(10) Nov 1991, 1056-1058.
- Meut, C., Bavoux, F., Cynober, E., & Lebrun, F. (1994). Necrotizing enterocolitis in a newborn: Maternal psychotropic drugs suspected: The Canadian Journal of Psychiatry / La Revue canadienne de psychiatrie Vol 39(2) Mar 1994, 127.
- Meyer, F. P., Walther, H., & Uchtlander, M. (1984). Effects of drugs on discrimination ability: Psychiatrie, Neurologie und Medizinische Psychologie Vol 36(8) Aug 1984, 464-471.
- Mihaljevic-Peles, A., Jakovljevic, M., Mrsic, M., & Sagud, M. (2001). Thrombocytopenia associated with clozapine and fluphenazine: Nordic Journal of Psychiatry Vol 55(6) 2001, 449-450.
- Minocha, K. B., Narang, R. L., & Agarwal, A. K. (1993). Prescribing pattern of psychotherapeutic drugs in patients admitted in psychiatry ward of an Indian hospital: Asia Pacific Journal of Pharmacology Vol 8(4) Dec 1993, 231-236.
- Minzi, A. L., Celeste, M. G., & Ciampini, M. (1985). Lormetazepam as a hypnoinducing drug: A multicenter national survey: Current Therapeutic Research Vol 38(2) Aug 1985, 183-195.
- Miyaoka, H., & Kamijima, K. (1999). Perphenazine-induced hiccups: Pharmacopsychiatry Vol 32(2) Mar 1999, 81.
- Mizuki, Y., Hirano, H., Miyoshi, A., Hamasaki, J., & et al. (1987). Residual effects of zopiclone on subsequent daytime functions in normal humans: Human Psychopharmacology: Clinical and Experimental Vol 2(2) Jun 1987, 119-126.
- Mizuki, Y., Suetsugi, M., Hotta, H., Ushijima, I., & et al. (1995). Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal humans: Progress in Neuro-Psychopharmacology & Biological Psychiatry Vol 19(3) May 1995, 385-401.
- Momose, T., Ishii, S., & Kuge, T. (1976). Controlled comparison of estazolam and nitrazepam as hypnotics on the preoperative night sleep: Current Therapeutic Research Vol 19(3) Mar 1976, 277-291.
- Monti, J. M., & Velluti, R. (1974). Action of psychotropic drugs upon pO-sub-2 in the lateral amygdala and pontine reticular formation during the sleep-wakefulness cycle: Pharmacology, Biochemistry and Behavior Vol 2(6) Nov-Dec 1974, 763-767.
- Morgan, H., Scott, D. F., & Joyce, C. R. (1970). The effects of four hypnotic drugs and placebo on normal subjects' sleeping and dreaming at home: British Journal of Psychiatry Vol 117(541) Dec 1970, 649-652.
- Morgan, K. (1985). Effects of repeated dose nitrazepam and lormetazepam on psychomotor performance in the elderly: Psychopharmacology Vol 86(1-2) May-Jun 1985, 209-211.
- Muraoka, M., Tada, K., Nogami, Y., Ishikawa, K., & et al. (1992). Residual effects of repeated administration of triazolam and nitrazepam in healthy volunteers: Neuropsychobiology Vol 25(3) 1992, 134-139.
- Nabeshima, T., Tohyama, K., Ichihara, K., & Kameyama, T. (1990). Effects of benzodiazepines on passive avoidance response and latent learning in mice: Relationship to benzodiazepine receptors and the cholinergic neuronal system: Journal of Pharmacology and Experimental Therapeutics Vol 255(2) Nov 1990, 789-794.
- Nakajima, R., & et al. (1971). Pharmacological studies on new potent central depressants, 8-chloro-6-phenyl-4H-s-triazolo -4,3a= -1,4= benzodiazepine (D-40TA) and its 1-methyl analogue (D-65MT): Japanese Journal of Pharmacology Vol 21(4) Aug 1971, 497-516.
- Nakamura, M., & Fukushima, H. (1976). Head twitches induced by benzodiazepines and the role of biogenic amines: Psychopharmacology Vol 49(3) 1976, 259-261.
- Nakanishi, M., & Setoguchi, M. (1972). Studies on psychotropic drugs: XX. Effects of 1-methyl-5-o-chlorophenyl-7-ethyl-1,2-dihydro-3H-thieno(2,3-e)(1,4)diazepin-2-one (Y-6047) on the metabolism of biogenic amines: Arzneimittel-Forschung Vol 22(11) Nov 1972, 1914-1918.
- Nakanishi, M., Yasuda, H., & Tsumagari, T. (1973). Protective effect of anti-anxiety drugs against hypoxia: Life Sciences Vol 13(5) Sep 1973, 467-474.
- Nakazawa, Y., & et al. (1975). Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives: Psychopharmacologia Vol 44(2) 1975, 165-171.
- Newton, J. R., Shapiro, C., & Stewart, A. (1989). Thirty years' war: A battle with insomnia: British Journal of Psychiatry Vol 154 May 1989, 691-696.
- Nicholson, A. N., & Wright, C. M. (1974). Inhibitory and disinhibitory effects of nitrazepam, diazepam and flurazepam hydrochloride on delayed matching behaviour in monkeys (Macaca mulatta): Neuropharmacology Vol 13(10-11) Nov 1974, 919-926.
- Nishikawa, T., & Nishioka, S. (2002). A case of Meige dystonia induced by short-term quetiapine treatment: Human Psychopharmacology: Clinical and Experimental Vol 17(4) Jun 2002, 197.
- Niwaguchi, T., Inoue, T., & Nakahara, Y. (1974). Studies of enzymatic dealkylation of D-lysergic acid diethylamide (LSD): Biochemical Pharmacology Vol 23(6) Mar 1974, 1073-1078.
- Nowakowska, E., & Chodera, A. (1991). Studies on the involvement of opioid mechanism in the locomotor effects of benzodiazepines in rats: Pharmacology, Biochemistry and Behavior Vol 38(2) Feb 1991, 265-266.
- Ogura, C., & et al. (1980). Residual effects of hypnotics: Triazolam, flurazepam, and nitrazepam: Psychopharmacology Vol 68(1) Apr 1980, 61-65.
- O'Hanlon, J. F., & Volkerts, E. R. (1986). Hypnotics and actual driving performance: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 95-104.
- Ornstein, P. H., & et al. (1969). Drugs and dreams: IV. Tranquilizers and their effects upon dreams and dreaming in schizophrenic patients: Experimental Medicine & Surgery Vol 27(1-2) 1969, 145-156.
- Peck, A. W., Adams, R., Bye, C., & Wilkinson, R. T. (1976). Residual effects of hypnotic drugs: Evidence for individual differences on vigilance: Psychopharmacology Vol 47(2) 1976, 213-216.
- Podhorna, J., & Krsiak, M. (2000). Behavioural effects of a benzodiazepine receptor partial agonist, Ro 19-8022, in the social conflict test in mice: Behavioural Pharmacology Vol 11(2) Apr 2000, 143-151.
- Pompeia, S., Gorenstein, C., & Curran, H. V. (1996). Benzodiazepine effects on memory tests: Dependence on retrieval cues? : International Clinical Psychopharmacology Vol 11(4) Dec 1996, 229-236.
- Pompeia, S., Gorenstein, C., & Curran, H. V. (1996). Does potency determine amnestic effects of benzodiazepines? A dose-response comparison of flunitrazepam and nitrazepam: Behavioural Pharmacology Vol 7(6) Nov 1996, 532-539.
- Pustorino, G., Spano, M., Sgro, D. L., Di Rosa, G., Tricomi, G., Bellantone, D., et al. (2007). Status gelasticus associated with levetiracetam as add-on treatment: Epileptic Disorders Vol 9(2) Jun 2007, 186-189.
- Rickels, K. (1986). The clinical use of hypnotics: Indications for use and the need for a variety of hypnotics: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 132-141.
- Roden, S., Harvey, P., & Mitchard, M. (1977). The influence of alcohol on the persistent effects on human performance of the hypnotics Mandrax and nitrazepam: International Journal of Clinical Pharmacology & Biopharmacy Vol 15(8) Aug 1977, 350-355.
- Rona-Dessalles, E., Sibboni, G., & Tignol, J. (1989). Benzodiazepines in the general hospital: An example of their use at the Perigueux Hospital Center: L'Encephale Vol 15(2) Mar-Apr 1989, 287-294.
- Rosenberg, J., & Geisler, A. (1994). The use of hypnotics in general practice: Nordic Journal of Psychiatry Vol 48(6) 1994, 429-433.
- Ross, N., & Monti, J. M. (1971). Effects of haloperidol, trifluperidol, nitrazepam and chlordiazepoxide upon conditioned midbrain behavioral responses: Psychopharmacologia Vol 22(1) 1971, 31-44.
- Rowlett, J. K., Lelas, S., Tornatzky, W., & Licata, S. C. (2006). Anti-conflict effects of benzodiazepines in rhesus monkeys: Relationship with therapeutic doses in humans and role of GABA-sub(A) receptors: Psychopharmacology Vol 184(2) Jan 2006, 201-211.
- Rudenko, G. M., Chemesov, Y. V., Garibova, T. L., & Voronina, T. A. (1983). Comparative characteristics of psychotropic activity of "atypical" tranquilizers under experimental conditions: Farmakologiya i Toksikologiya Vol 46(3) 1983, 26-29.
- Saario, I., Linnoila, M., & Maki, M. (1975). Interaction of drugs with alcohol on human psychomotor skills related to driving: Effect of sleep deprivation or two weeks' treatment with hypnotics: Journal of Clinical Pharmacology Vol 15(1, Pt 1) Jan 1975, 52-59.
- Salt, J. S., & Taberner, P. V. (1984). Differential effects of benzodiazepines and amphetamine on exploratory behaviour in weanling rats: An animal model for anxiolytic activity: Progress in Neuro-Psychopharmacology & Biological Psychiatry Vol 8(1) 1984, 163-169.
- Sambrooks, J. E., MacCulloch, M. J., & Rooney, J. F. (1975). The automated assessment of the effect of flurazepam and nitrazepam on mood state: Acta Psychiatrica Scandinavica Vol 51(3) Mar 1975, 201-209.
- Sarbulescu, A., Alexandrescu, L., & Georgescu, M.-J. (1986). Comparative study of two benzodiazepines ("diazepam" versus "nitrazepam") in the treatment of postneuroleptic tardive dyskinesia: Revue Roumaine de Neurologie et Psychiatrie Vol 24(3) Jul-Sep 1986, 189-193.
- Satija, D. C., Natani, G. D., Purohit, D. R., Gaur, R., & et al. (1988). A double blind comparative study of usefulness of clonidine and symptomatic therapy in opiate detoxification: Indian Journal of Psychiatry Vol 30(1) Jan 1988, 55-59.
- Sato, K., & et al. (1985). Pharmacologic studies of central actions of zopiclone: Influence on brain monoamines in rats under stressful condition: International Journal of Clinical Pharmacology, Therapy & Toxicology Vol 23(4) Apr 1985, 204-210.
- Schuler, M., Gaillard, J. M., & Tissot, R. (1972). Comparison of the sleep-inducing effect of Ro 5-4200 and nitrazepam: Psychopharmacologia Vol 27(2) 1972, 123-130.
- Singer, K., Lo, C. W., & Tam, Y. K. (1978). Comparative evaluation of hypnotic efficacy of flunitrazepam in psychiatric in-patients: Acta Psychiatrica Scandinavica Vol 57(5) May 1978, 382-388.
- Smirne, S., Franceschi, M., & Comi, G. (1974). Rapid EEG activity after single doses of sleep-inducing drugs in normal subjects: Rivista Sperimentale di Freniatria e Medicina Legale delle Alienazioni Mentali Vol 98(6) Dec 1974, 1189-1193.
- Spencer, G., & Yuvarajan, R. (1995). Psychotic symptoms after benzodiazepine withdrawal: International Journal of Geriatric Psychiatry Vol 10(10) Oct 1995, 901-902.
- Suetsugi, M., Mizuki, Y., Yamamoto, K., Uchida, S., & Watanabe, Y. (2007). The effect of placebo administration on the first-night effect in healthy young volunteers: Progress in Neuro-Psychopharmacology & Biological Psychiatry Vol 31(4) May 2007, 839-847.
- Sulcova, A., & Krsiak, M. (1989). Differences among nine 1,4-benzodiazepines: An ethopharmacological evaluation in mice: Psychopharmacology Vol 97(2) Feb 1989, 157-159.
- Tada, K., Sato, Y., Sakai, T., Ueda, N., & et al. (1994). Effects of zopiclone, triazolam, and nitrazepam on standing steadiness: Neuropsychobiology Vol 29(1) Jan 1994, 17-22.
- Tazaki, T., Tada, K., Nogami, Y., Takemura, N., & et al. (1989). Effects of butoctamide hydrogen succinate and nitrazepam on psychomotor function and EEG in healthy volunteers: Psychopharmacology Vol 97(3) Mar 1989, 370-375.
- Terao, T., Oga, T., Furukawa, T., Nozaki, S., & et al. (1994). Antiaggressive effect of lithium: Lithium withdrawal study of patients with mental retardation: Seishin Igaku (Clinical Psychiatry) Vol 36(10) Oct 1994, 1071-1076.
- Terao, T., Yoshimura, R., Terao, M., & Abe, K. (1992). Depersonalization following nitrazepam withdrawal: Biological Psychiatry Vol 31(2) Jan 1992, 212-213.
- Thiebot, M. H., le Bihan, C., Soubrie, P., & Simon, P. (1986). Reduced waiting capacities as a possible mechanism of action of benzodiazepines: Hypotheses derived from their behavioral effects in animals: L'Encephale Vol 12(3) May-Jun 1986, 93-97.
- Thiebot, M.-H., le Bihan, C., Soubrie, P., & Simon, P. (1985). Benzodiazepines reduce the tolerance to reward delay in rats: Psychopharmacology Vol 86(1-2) May-Jun 1985, 147-152.
- Tosi, G. C., Tosi, E. C., & Hattab, J. R. (1973). The use of N-demethyldiazepam in outpatients suffering from insomnia: Current Therapeutic Research Vol 15(7) Jul 1973, 460-464.
- Van, H. L., & Zitman, F. G. (1987). Prescription of benzodiazepines to psychiatric outpatients: Tijdschrift voor Alcohol, Drugs en Andere Psychotrope Stoffen Vol 13(5) Oct 1987, 157-163.
- Van, H. L., & Zitman, F. G. (1988). The evidence of benzodiazepine dependence: Tijdschrift voor Alcohol, Drugs en Andere Psychotrope Stoffen Vol 14(4) Sep 1988, 148-155.
- Vermeeren, A. (2004). Residual Effects of Hypnotics: Epidemiology and Clinical Implications: CNS Drugs Vol 18(5) 2004, 297-328.
- Vikhlyaev, Y. I., & Klygul, T. A. (1971). Activating component in the effect produced by the benzodiazepine series of tranquilizers: Farmakologiya i Toksikologiya Vol 34(3) May 1971, 268-272.
- Vikhlyaev, Y. I., & Klygul, T. A. (1973). The influence of tranquilizers of the benzodiazepine series on various forms of operant behavior in animals: Farmakologiya i Toksikologiya Vol 36(6) Nov 1973, 657-663.
- Vikhlyaev, Y. I., Klygul, T. A., & Astakhova, A. V. (1970). On the anticonvulsant properties of several benzodiazepine derivatives: Farmakologiya i Toksikologiya Vol 33(2) 1970, 149-154.
- Vikhlyaev, Y. I., Klygul, T. A., Prokudin, V. N., & Andronati, S. A. (1971). Comparison of the actional features of tranquilizers under experimental conditions and in clinical practice: Farmakologiya i Toksikologiya Vol 34(1) Jan 1971, 30-35.
- Vikhlyaev, Y. I., Lando, L. I., & Segal, A. M. (1974). The effect of diazepam and nitrazepam upon the intra- and extracellular distribution of sodium and potassium ions in individual structures of the rat's brain: Farmakologiya i Toksikologiya Vol 37(1) Jan 1974, 10-14.
- Vinader-Caerols, C., Brain, P. F., Parra, A., & Simon, V. M. (1992). An ethological analysis of the effects of diazepam and nitrazepam on the responses of female mice to anosmic males encountered in a novel arena: Behavioural Pharmacology Vol 3(5) Oct 1992, 427-433.
- Vinarova, E., & Cinek, O. (1985). Drugs used in a home for the elderly: Activitas Nervosa Superior Vol 27(4) Dec 1985, 268.
- Viukari, M., Jaatinen, P., & Kylmamaa, T. (1983). Flunitrazepam, nitrazepam and pyschomotor skills in psychogeriatric patients: Current Therapeutic Research Vol 33(5) May 1983, 828-834.
- Viukari, M., Linnoila, M., & Aalto, U. (1978). Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients: Acta Psychiatrica Scandinavica Vol 57(1) Jan 1978, 27-35.
- Viukari, M., Vartio, T., & Verho, E. (1984). Low doses of brotizolam and nitrazepam as hypnotics in the elderly: Neuropsychobiology Vol 12(2-3) 1984, 130-133.
- Volavka, J. V., & et al. (1969). Effect of nitrazepam, amylobarbitone sodium and placebo on the electroencephalogram of normal subjects: Psychopharmacologia 14(3) 1969, 178-183.
- Wheatley, D. (1985). Insomnia in the community: The patient who cannot sleep: Psychiatria Fennica Suppl 1985, 174-180.
- Wheatley, D. (1986). Brotizolam: A new short-acting hypnotic: International Clinical Psychopharmacology Vol 1(1) Jan 1986, 36-44.
- Wheatley, D. (1986). Insomnia in general practice: The role of temazepam and a comparison with zopiclone: Acta Psychiatrica Scandinavica Vol 74(332, Suppl) 1986, 142-148.
- Yamashita, Y., Matsuishi, T., Murakami, Y., & Kato, H. (1999). Sleep disorder in Rett syndrome and melatonin treatment: Brain & Development Vol 21(8) Dec 1999, 570.
- Yanagita, T. (1982). Dependence potential of zopiclone studied in monkeys: International Pharmacopsychiatry Vol 17(Suppl 2) 1982, 216-227.
- Zakusov, V. V., & Ostrovskaya, R. U. (1971). Increase in the resistance of mice to hypoxia under the influence of tranquilizers of the benzodiazepine series: Byulleten' Eksperimental'Noi Biologii i Meditsiny Vol 71(2) Feb 1971, 45-47.
- Zou, L.-P., Ding, C.-H., Fang, F., Sin, N.-c., & Mix, E. (2006). Prospective Study of First-choice Topiramate Therapy in Newly Diagnosed Infantile Spasms: Clinical Neuropharmacology Vol 29(6) Nov-Dec 2006, 343-349.
Benzodiazepines (N05BA, N05CD)
Bromazepam • Camazepam • Carburazepam • Chlordiazepoxide • Cinolazepam • Clonazepam • Clorazepate • Cyprazepam • Delorazepam • Demoxepam • Diazepam • Doxefazepam • Elfazepam • Ethyl carfluzepate • Ethyl dirazepate • Ethyl loflazepate • Fletazepam • Fludiazepam • Flunitrazepam • Flurazepam • Flutemazepam • Flutoprazepam • Fosazepam • Gidazepam • Halazepam • Iclazepam • Lopirazepam • Lorazepam • Lormetazepam • Meclonazepam • Medazepam • Menitrazepam • Metaclazepam • Motrazepam • Nimetazepam • Nitrazepam • Nitrazepate • Nordazepam • Nortetrazepam • Oxazepam • Phenazepam • Pinazepam • Pivoxazepam • Prazepam • Proflazepam • Quazepam • QH-II-66 • Reclazepam • Sulazepam • Temazepam • Tetrazepam • Tolufazepam • Tuclazepam • Uldazepam