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{| border="1" cellpadding="2" cellspacing="0" align="right" width="250px" style="border-collapse: collapse; margin: 0 0 0 0.5em"
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|-
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| bgcolor="#ffffff" align="center" colspan="2" | [[Image:dextromethorphan.png|250px|Molecular structure of dextromethorphan]]<br/>''Dextromethorphan''
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|-
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| align="center" colspan="2" | <small>D</small>-(+)''-3-methoxy-17-methyl-<br/>(9&alpha;,13&alpha;,14&alpha;)-morphinan''
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|- align="center" style="border-bottom: 2px solid gray"
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| '''[[CAS number]]''' <br /> 125-71-3
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| '''[[ATC code]]''' <br /> R05DA09
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|-
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| bgcolor="#eeeeee" | [[Chemical formula]]
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| bgcolor="#ddeeff" | [[Carbon|C]]<sub>18</sub>[[Hydrogen|H]]<sub>25</sub>[[Nitrogen|N]][[Oxygen|O]]
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|-
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| bgcolor="#eeeeee" | [[Molecular weight]]
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| bgcolor="#ddeeff" | 271.4
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|-
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| bgcolor="#eeeeee" | [[Bioavailability]]
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| bgcolor="#ddeeff" | ?
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|-
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| bgcolor="#eeeeee" | Metabolism
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| bgcolor="#ddeeff" | hepatic
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|-
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| bgcolor="#eeeeee" | [[Elimination half-life]]
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| bgcolor="#ddeeff" | 3 to 6 hours
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|-
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| bgcolor="#eeeeee" | [[Excretion]]
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| bgcolor="#ddeeff" | ?
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|-
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| bgcolor="#eeeeee" | [[Pregnancy category (pharmaceutical)|Pregnancy category]]
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| bgcolor="#ddeeff" | C ([[United States]])<br>A ([[Australia]])
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|-
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| bgcolor="#eeeeee" | [[Regulation of therapeutic goods|Legal status]]
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| bgcolor="#ddeeff" | Schedule 2 ([[Australia]])
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|-
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| bgcolor="#eeeeee" | Route of administration
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| bgcolor="#ddeeff" | Oral
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|-
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|}
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{| bgcolor="#ffffff" border="1" cellpadding="3" cellspacing="0" align="right" wordwrap="tight" width="167px" style="border-collapse: collapse; clear: right; margin: 0 0 0 0.5em"
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|-
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| '''Indications:'''
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* Non-productive [[Cough]]
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|-
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| '''Contraindications:'''
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* Individuals with a known hypersensitivity to dextromethorphan
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* Patients receiving [[MAOI]] therapy
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* [[Atopic]] patients
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|-
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|'''[[non-medical use of dextromethorphan|Non-medical Uses]]:'''
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*[[Psychedelics, dissociatives and deliriants|Hallucinogen]]
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*[[Dissociative]]
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|-
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|}
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'''Dextromethorphan''' ('''DM''' or '''DXM''') is an [[antitussive]] drug that is found in many [[Over-the-counter_substance|over-the-counter]] [[common cold|cold]] and [[cough syrup|cough]] preparations, usually in the form of dextromethorphan hydrobromide.
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==Chemistry==
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Dextromethorphan is a [[salt]] of the methyl ether [[dextrorotatory]] [[isomer]] of levorphanol, a [[opioid|narcotic]] [[analgesic]]. It is chemically named as ''3-methoxy-17-methyl-9(alpha), 13(alpha), 14(alpha)-morphinan hydrobromide monohydrate''. DM occurs as white [[crystals]], is sparingly soluble in water, and freely soluble in [[ethanol|alcohol]]. The drug is [[dextrorotation|dextrorotatory]] in water (at 20 degrees [[Celsius]], Sodium D-line) with a specific rotation of +27.6 degrees.
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Dextromethorphan is metabolized by various liver [[enzyme]]s and subsequently undergoes O-demethylation, N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. Hours after dextromethorphan therapy, (in humans) the metabolites (+)-3-hydroxy-N-methylmorphinan, (+)-3-morphinan, and traces of the unchanged drug are detectable in the [[urine]].
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== Indications ==
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The FDA approved dextromethorphan for over-the-counter sale as an cough suppressant in 1958. This filled the need for a cough suppressant lacking the abuse liability and addictive properties of [[codeine]] phosphate, the most widely used cough medication at the time. The advantage of dextromethorphan preparations over those containing codeine (now prescription only in the [[United States]]) was the lack of physical addiction potential and sedative side-effects.
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== Pharmacodynamics ==
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At therapeutic doses, the drug acts [[central nervous system|centrally]] to elevate the threshold for coughing, without inhibiting [[cilia|ciliary]] activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, and exerts its activity within 15 to 60 minutes of ingestion. The duration of action after oral administration is approximately three to eight hours. Because administration of DM can be accompanied by [[histamine]] release, its use in [[atopic]] children is very limited.
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The average dosage necessary for effective antitussive therapy is between 10mg and 30mg every four to six hours.
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According to the [[World Health Organization|WHO]] committee on Drug Dependence, dextromethorphan, when used recreationally (see [[non-medical use of dextromethorphan]]), doesn't produce [[addiction|physical addiction]] but can generate slight psychological dependence in some users.
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== Clinical pharmacology ==
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Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the [[blood-brain barrier]]. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active [[metabolite]] of dextromethorphan, [[dextrorphan]], the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is predominantly metabolized by the [[liver]], by various hepatic enzymes. Through various pathways, the drug undergoes (O-demethylation (which produces dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. The inactive metabolite (+)-3-hydroxy-N-methylmorphinan is formed as a product of DM metabolism by these pathways. One well known metabolic catalyst involved is a specific [[cytochrome P450]] [[enzyme]] known as 2D6, or [[CYP2D6]]. A significant portion of the population has a functional deficiency in this enzyme (and are known as poor CYP2D6 metabolizers). As CYP2D6 is the primary [[metabolic pathway]] in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan are significantly increased in such poor metabolizers. Deaths and hospitalizations have been reported in recreational use by poor CYP2D6 metabolizers.
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A large number of medications (including [[antidepressant]]s) are potent inhibitors of CYP2D6 ''(see [[CYP2D6]] article)''. There exists, therefore, the potential of drug-drug interactions between dextromethorphan and concomitant medications. There have been reports of fatal consequences arising from such interactions.
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Dextromethorphan crosses the [[blood-brain barrier]], and the following pharmacological actions have been reported:
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* [[NMDA receptor|NMDA]] [[glutamate|glutamatergic]] [[receptor antagonist]]
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* [[Dopamine]] [[reuptake]] inhibitor
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* [[Sigma-1 receptor|&sigma;<sub>1</sub>]] and [[Sigma-2 receptor|&sigma;<sub>2</sub>]] receptor agonist (Zhou & Musacchio, 1991)
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* &alpha;3&beta;4 [[Nicotinic acetylcholine receptor|nicotinic]] receptor antagonist [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10869398]
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* [[Serotonin]] [[reuptake]] inhibitor [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1636059]
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== History ==
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Dextromethorphan was first patented with {{US patent|2,676,177}}, and was approved for over-the-counter purchase as an antitussive in [[1958]].
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==Non-Medical Use==
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For a history of and information on the use of dextromethorphan as a dissociative or hallucinogen, see [[non-medical use of dextromethorphan]].
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[[Category:Antitussives]]
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[[Category:Dissociatives]]
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[[Category:Dopamine reuptake inhibitors]]
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[[Category:NMDA receptor antagonists]]
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[[Category:Over-the-counter substances]]
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[[Category:Sigma agonists]]
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[[de:Dextromethorphan]]
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[[fr:Dextrométhorphan]]
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[[es:Dextrometorfano]]
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[[hu:Dextromethorphan]]
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[[nl:Dextromethorphan]]
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[[pl:Dekstrometorfan]]
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[[fi:Dekstrometorfaani]]
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[[zh:DXM]]
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{{enWP|Dextromethorphan}}

Latest revision as of 22:54, February 25, 2007

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Dextromethorphan
Dextromethorphan
D-(+)-3-methoxy-17-methyl-
(9α,13α,14α)-morphinan
CAS number
125-71-3
ATC code
R05DA09
Chemical formula C18H25NO
Molecular weight 271.4
Bioavailability  ?
Metabolism hepatic
Elimination half-life 3 to 6 hours
Excretion  ?
Pregnancy category C (United States)
A (Australia)
Legal status Schedule 2 (Australia)
Route of administration Oral
Indications:
Contraindications:
  • Individuals with a known hypersensitivity to dextromethorphan
  • Patients receiving MAOI therapy
  • Atopic patients
Non-medical Uses:

Dextromethorphan (DM or DXM) is an antitussive drug that is found in many over-the-counter cold and cough preparations, usually in the form of dextromethorphan hydrobromide.

ChemistryEdit

Dextromethorphan is a salt of the methyl ether dextrorotatory isomer of levorphanol, a narcotic analgesic. It is chemically named as 3-methoxy-17-methyl-9(alpha), 13(alpha), 14(alpha)-morphinan hydrobromide monohydrate. DM occurs as white crystals, is sparingly soluble in water, and freely soluble in alcohol. The drug is dextrorotatory in water (at 20 degrees Celsius, Sodium D-line) with a specific rotation of +27.6 degrees.

Dextromethorphan is metabolized by various liver enzymes and subsequently undergoes O-demethylation, N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. Hours after dextromethorphan therapy, (in humans) the metabolites (+)-3-hydroxy-N-methylmorphinan, (+)-3-morphinan, and traces of the unchanged drug are detectable in the urine.

Indications Edit

The FDA approved dextromethorphan for over-the-counter sale as an cough suppressant in 1958. This filled the need for a cough suppressant lacking the abuse liability and addictive properties of codeine phosphate, the most widely used cough medication at the time. The advantage of dextromethorphan preparations over those containing codeine (now prescription only in the United States) was the lack of physical addiction potential and sedative side-effects.

Pharmacodynamics Edit

At therapeutic doses, the drug acts centrally to elevate the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, and exerts its activity within 15 to 60 minutes of ingestion. The duration of action after oral administration is approximately three to eight hours. Because administration of DM can be accompanied by histamine release, its use in atopic children is very limited.

The average dosage necessary for effective antitussive therapy is between 10mg and 30mg every four to six hours.

According to the WHO committee on Drug Dependence, dextromethorphan, when used recreationally (see non-medical use of dextromethorphan), doesn't produce physical addiction but can generate slight psychological dependence in some users.

Clinical pharmacology Edit

Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is predominantly metabolized by the liver, by various hepatic enzymes. Through various pathways, the drug undergoes (O-demethylation (which produces dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. The inactive metabolite (+)-3-hydroxy-N-methylmorphinan is formed as a product of DM metabolism by these pathways. One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6. A significant portion of the population has a functional deficiency in this enzyme (and are known as poor CYP2D6 metabolizers). As CYP2D6 is the primary metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan are significantly increased in such poor metabolizers. Deaths and hospitalizations have been reported in recreational use by poor CYP2D6 metabolizers.

A large number of medications (including antidepressants) are potent inhibitors of CYP2D6 (see CYP2D6 article). There exists, therefore, the potential of drug-drug interactions between dextromethorphan and concomitant medications. There have been reports of fatal consequences arising from such interactions.

Dextromethorphan crosses the blood-brain barrier, and the following pharmacological actions have been reported:

History Edit

Dextromethorphan was first patented with U.S. Patent 2,676,177  , and was approved for over-the-counter purchase as an antitussive in 1958.

Non-Medical UseEdit

For a history of and information on the use of dextromethorphan as a dissociative or hallucinogen, see non-medical use of dextromethorphan.de:Dextromethorphan fr:Dextrométhorphan es:Dextrometorfano hu:Dextromethorphan nl:Dextromethorphanfi:Dekstrometorfaani zh:DXM

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