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{{BioPsy}}
 
{{Drugbox|
 
{{Drugbox|
 
|IUPAC_name = ''methyl-11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl)<br>
 
|IUPAC_name = ''methyl-11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl)<br>
 
''oxy]-3β,20α-yohimban-16β-carboxylate''{{ref|iupac}}
 
''oxy]-3β,20α-yohimban-16β-carboxylate''{{ref|iupac}}
| image={{PAGENAME}}.png
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| image=Reserpine.png
 
| CAS_number=50-55-5
 
| CAS_number=50-55-5
 
| ATC_prefix=C02
 
| ATC_prefix=C02
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| PubChem=5770
 
| PubChem=5770
 
| DrugBank=APRD00472
 
| DrugBank=APRD00472
| chemical_formula = C<sub>33</sub>H<sub>40</sub>N<sub>2</sub>O<sub>9</sub>
+
| C=33 | H=40 | N=2 | O=9
| molecular_weight = 608.679 g/mol
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| molecular_weight = 608.68 g/mol
 
| bioavailability= 50%
 
| bioavailability= 50%
 
| metabolism = gut/liver
 
| metabolism = gut/liver
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| pregnancy_category = D (fetotoxic)
 
| pregnancy_category = D (fetotoxic)
 
| legal_status = Rx-only (some countries banned/discontinued)
 
| legal_status = Rx-only (some countries banned/discontinued)
  +
| licence_US = Reserpine
 
| routes_of_administration= oral
 
| routes_of_administration= oral
 
}}
 
}}
'''Reserpine''' is an [[indole]] [[alkaloid]]{{ref|indole-alkaloid}} [[antipsychotic]] and [[antihypertensive]] drug known to irreversibly bind to storage [[vesicle]]s of [[neurotransmitter]]s such as [[dopamine]], [[norepinephrine]], and [[serotonin]].{{ref|veterinary1}} Reserpine depletion of monoamine neurotransmitters in the synapses is often used to bolster the theory that depletion of the neurotransmitters causes subsequent [[clinical depression|depression]] in humans. However a 1950's drug trial at Maudsley Hospital found that in fact reserpine, far from causing depression, actually acted as an antidepressant. Moreover, reserpine has a peripheral action in many parts of the body, resulting in a preponderance of the cholinergic part of the nervous system (GI-Tract, smooth muscles vessels).
+
'''Reserpine''' is an [[indole]] [[alkaloid]]{{ref|indole-alkaloid}} [[antipsychotic]] and [[antihypertensive]] drug that has been used for the control of [[hypertension|high blood pressure]] and for the relief of [[psychotic]] behaviors, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.<ref> [http://www.bartleby.com/65/re/reserpin.html] The Columbia Encyclopedia, Sixth Edition. Copyright © 2001-05 Columbia University Press. </ref> The antihypertensive actions of Reserpine are a result of its ability to deplete [[catecholamine]]s (among the others) from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance. .{{ref|veterinary1}} Reserpine depletion of monoamine [[neurotransmitter]]s in the [[synapse]]s is often cited as evidence to the theory that depletion of the neurotransmitters causes subsequent [[clinical depression|depression]] in humans. Moreover, reserpine has a peripheral action in many parts of the body, resulting in a preponderance of the cholinergic part of the nervous system (GI-Tract, smooth muscles vessels).
  +
  +
==Mode of action==
  +
Reserpine acts by blocking the vesicular monoamine transporter [[VMAT]], which normally transports free [[norepinephrine]], [[serotonin]], and [[dopamine]] from the cytoplasm of the presynaptic nerve into vesicles for subsequent release into the [[synaptic cleft]]. The unprotected neurotransmitters are then metabolized by [[MAO]] and therefore never reach the synapse. <ref> Ellenhorn & Barceloux , 1989; Gilman et al, 1990. </ref>
   
 
==History==
 
==History==
Reserpine was isolated in 1952 from the dried root of ''[[Rauwolfia serpentina]]'' (Indian [[snakeroot]]),{{ref|mercksource}} and introduced in 1954, two years after [[chlorpromazine]].{{ref|history1}}
+
Reserpine was isolated in 1952 from the dried root of ''[[Rauwolfia serpentina]]'' (Indian [[snakeroot]]),{{ref|mercksource}} (which had been known as ''Sarpaganda'' and had been used for centuries there for the treatment of insanity, as well as fever and snakebites<ref> Op. cit. Columbia Encyclopedia </ref> — even [[Mahatma Gandhi]] used it as a [[tranquilizer]] during his lifetime.<ref>[http://www.time.com/time/magazine/article/0,9171,857672,00.html Pills for Mental Illness?], ''[[TIME Magazine]]'', November 8, 1954</ref>) and introduced in [[1954]], two years after [[chlorpromazine]].{{ref|history1}} Reserpine almost irreversibly blocks the uptake (and storage) of [[norepinephrine]] (i.e. [[noradrenaline]]) and [[dopamine]] into synaptic vesicles by inhibiting the Vesicular Monoamine Transporters ([[VMAT]]).{{ref|VMAT}}
Reserpine almost irreversibly blocks the accumulation of noradrenaline and dopamine into synaptic vesicles by inhibiting the Vesicular Monoamine Transporters (VMAT). [Schuldiner, S. et al. ''J. Biol. Chem.'' '''1993''' (268:1) 29-34]
 
   
 
Reserpine has been discontinued in the UK for some years due to its vast interactions and side effects.
 
Reserpine has been discontinued in the UK for some years due to its vast interactions and side effects.
  +
  +
Reserpine was also highly influential in promoting the thought of a biogenic-amine hypothesis of depression - see Everett & Tolman, 1959.
   
 
==Uses today==
 
==Uses today==
In some countries reserpine is still available as part of combination drugs for the treatment of hypertension, in most cases they contain also a diuretic and/or a vasodilator like hydralazine. These combinations are currently regarded as second choice drugs. The daily dose of reserpine in antihyertensive treatment is as low as 0.1 to 0.25mg. The use of reserpine as antipsychotic drug has been nearly completely abandoned. Originally, 0.5mg to 40mg daily were used to treat psychotic diseases. Doses in excess of 3mg daily often required use of an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism. Reserpine may be used as a sedative for horses.
+
Reserpine is one of the few antihypertensive medications that have been shown in [[randomized controlled trials]] to reduce mortality: The Hypertension Detection and Follow-up Program,<ref name="pmid490882">{{cite journal |author= |title=Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group |journal=JAMA |volume=242 |issue=23 |pages=2562–71 |year=1979 |pmid=490882 |doi=}} [http://gateway.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=490882.ui full text at OVID]</ref> the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents,<ref name="pmid4862069">{{cite journal |author= |title=Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg |journal=JAMA |volume=202 |issue=11 |pages=1028–34 |year=1967 |pmid=4862069 |doi=}}</ref> and the Systolic Hypertension in the Elderly Program.<ref name="pmid2046107">{{cite journal |author= |title=Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group |journal=JAMA |volume=265 |issue=24 |pages=3255–64 |year=1991 |pmid=2046107 |doi=}}</ref>
  +
  +
Reserpine is listed as a second line choice by the [[JNC 7]].<ref name="pmid12748199">{{cite journal |author=Chobanian AV, Bakris GL, Black HR, ''et al'' |title=The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report |journal=JAMA |volume=289 |issue=19 |pages=2560–72 |year=2003 |pmid=12748199 |doi=10.1001/jama.289.19.2560}} [http://www.hypertensiononline.org/slides2/slide01.cfm?tk=15&pg=1 summary]</ref> Reserpine is a second-line adjunct agent for patients who are uncontrolled on a diuretic when cost is an issue.<ref name="pmid3592424">{{cite journal |author=Moser M |title="Cost containment" in the management of hypertension |journal=Ann. Intern. Med. |volume=107 |issue=1 |pages=107–9 |year=1987 |pmid=3592424 |doi=}}</ref>
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It is also used to treat symptoms of [[dyskinesia]] in patients sufferring from [[Huntington's disease]].<ref name=pharmnemonics>{{Cite book | author=Shen, Howard | title=Illustrated Pharmacology Memory Cards: PharMnemonics | date=2008 | publisher=Minireview | isbn=1-59541-101-1 | pages=11}}</ref>
  +
  +
In some countries reserpine is still available as part of combination drugs for the treatment of hypertension, in most cases they contain also a diuretic and/or a vasodilator like [[hydralazine]]. These combinations are currently regarded as second choice drugs. The daily dose of reserpine in antihypertensive treatment is as low as 0.1 to 0.25mg. The use of reserpine as an antipsychotic drug has been nearly completely abandoned. Originally, doses of 0.5mg to 40mg daily were used to treat psychotic diseases. Doses in excess of 3mg daily often required use of an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism. Reserpine may be used as a sedative for horses.
   
 
==Side effects==
 
==Side effects==
Reserpine has a high index and severity of side-effects. Often nausea, vomiting, gastric intolerance, gastric ulceration (due to increased cholinergic activity in gastric tissue and impaired mucosal quality), stomach cramps and diarrhea are noted. Otherwise, weight gain can been seen. The drug causes hypotension and bradycardia and may worsen asthma. Congested nose is another consequence of alpha-blockade. Depression does occur and may be severe enough to lead to suicide. Other central effects are a high incidence of drowsiness, dizziness, and nightmares. Parkinsonism occurs in a dose dependent manner. General weakness or fatigue is quite often encountered. High dose studies in rodents found reserpine to cause fibroadenoma of the breast and malignant tumors of the semen vesicles among others. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed.
+
At doses of less than 0.2 mg/day, reserpine has few side effects, most commonly is nasal congestion.<ref name="pmid3350594">{{cite journal |author=Curb JD, Schneider K, Taylor JO, Maxwell M, Shulman N |title=Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program |journal=Hypertension |volume=11 |issue=3 Pt 2 |pages=II51–5 |year=1988 |pmid=3350594 |doi=}}</ref>
  +
  +
There has been much concern about reserpine causing depression leading to suicide. However, this was reported in uncontrolled studies using doses averaging 0.5 mg per day.<ref name="pmid13629798">{{cite journal |author=QUETSCH RM, ACHOR RW, LITIN EM, FAUCETT RL |title=Depressive reactions in hypertensive patients; a comparison of those treated with Rauwolfia and those receiving no specific antihypertensive treatment |journal=Circulation |volume=19 |issue=3 |pages=366–75 |year=1959 |pmid=13629798 |doi=}}</ref><ref name="pmid13304797">{{cite journal |author=LEMIEUX G, DAVIGNON A, GENEST J |title=Depressive states during Rauwolfia therapy for arterial hypertension; a report of 30 cases |journal=Canadian Medical Association journal |volume=74 |issue=7 |pages=522–6 |year=1956 |pmid=13304797 |doi=}}</ref>
  +
  +
Reserpine can cause: nasal congestion, nausea, vomiting, weight gain, gastric intolerance, gastric ulceration (due to increased cholinergic activity in gastric tissue and impaired mucosal quality), stomach cramps and diarrhea are noted. The drug causes hypotension and bradycardia and may worsen asthma. Congested nose and erectile dysfunction are other consequences of alpha-blockade. Depression can occur at any dose and may be severe enough to lead to suicide. Other central effects are a high incidence of drowsiness, dizziness, and nightmares. Parkinsonism occurs in a dose dependent manner. General weakness or fatigue is quite often encountered. High dose studies in rodents found reserpine to cause fibroadenoma of the breast and malignant tumors of the seminal vesicles among others. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed. Besides, it may also cause [[hyperprolactinemia]].
   
 
==References==
 
==References==
*[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=148558&namedisopt=&ncount=165#Synonyms PubChem Substance Summary: Reserpine] National Center for Biotechnology Information.
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{{reflist}}
# {{note|iupac}} [http://homepage1.nifty.com/nomenclator/triv/alka_t-z.htm アルカロイド (Alkaloids) (T-Z)] 25 November 2004.
+
# {{note|indole-alkaloid}} [http://waynesword.palomar.edu/chemid2.htm#indole "Indole Alkaloids"] ''Major Types Of Chemical Compounds In Plants & Animals Part II: Phenolic Compounds, Glycosides & Alkaloids.'' Wayne's Word: An On-Line Textbook of Natural History. 2 May 2005. Accessed 1 September 2005.
+
==Footnotes==
  +
# {{note|iupac}} [http://homepage1.nifty.com/nomenclator/triv/alka_t-z.htm アルカロイド (Alkaloids) (T-Z)]. 2004.
  +
# {{note|indole-alkaloid}} [http://waynesword.palomar.edu/chemid2.htm#indole "Indole Alkaloids"] ''Major Types Of Chemical Compounds In Plants & Animals Part II: Phenolic Compounds, Glycosides & Alkaloids.'' Wayne's Word: An On-Line Textbook of Natural History. 2005.
 
# {{note|veterinary1}} Forney, Barbara. [http://www.wedgewoodpharmacy.com/monographs/reserpine.asp Reserpine for Veterinary Use] Wedgewood Pharmacy. 2001-2002.
 
# {{note|veterinary1}} Forney, Barbara. [http://www.wedgewoodpharmacy.com/monographs/reserpine.asp Reserpine for Veterinary Use] Wedgewood Pharmacy. 2001-2002.
 
# {{note|mercksource}} [http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_r_03zPzhtm#1093125 Rauwolfia] Dorlands Medical Dictionary. Merck Source. 2002.
 
# {{note|mercksource}} [http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_r_03zPzhtm#1093125 Rauwolfia] Dorlands Medical Dictionary. Merck Source. 2002.
# {{note|history1}} Lopez-Munoz F, Bhatara VS, Alamo C, Cuenca E. "[Historical approach to reserpine discovery and its introduction in psychiatry]" [Article in Spanish] ''Actas Esp Psiquiatr.'' 2004 Nov-Dec;32(6):387-95. PMID 15529229 [http://www.arsxxi.com/Revistas/mostrararticulo.php?idarticulo=411106110 Fulltext in English and Spanish]
+
# {{note|history1}} Lopez-Munoz F, Bhatara VS, Alamo C, Cuenca E. (2004): "[Historical approach to reserpine discovery and its introduction in psychiatry]" [Article in Spanish] ''Actas Esp Psiquiatr.'' 32(6):387-95. PMID 15529229 [http://www.arsxxi.com/Revistas/mostrararticulo.php?idarticulo=411106110 Fulltext in English and Spanish]
  +
# {{note|VMAT}}Schuldiner, S. et al. (1993): ''J. Biol. Chem.'' 268(1) 29-34. PMID 8416935
   
 
== External links ==
 
== External links ==
  +
*[http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+50-55-5 NLM Hazardous Substances Databank &ndash; Reserpine]
  +
*[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=148558&namedisopt=&ncount=165#Synonyms PubChem Substance Summary: Reserpine] National Center for Biotechnology Information.
 
*[http://www.organic-chemistry.org/Highlights/2006/01May.shtm The Stork Synthesis of (-)-Reserpine]
 
*[http://www.organic-chemistry.org/Highlights/2006/01May.shtm The Stork Synthesis of (-)-Reserpine]
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{{Adrenergic antagonist}}
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{{Antihypertensives and diuretics}}
   
 
[[Category:Alkaloids]]
 
[[Category:Alkaloids]]
[[Category:Antipsychotics]]
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[[Category:Antihypertensive drugs]]
[[Category:Indole compounds]]
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[[Category:Neuroleptic drugs]]
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[[Category:Sedatives]]
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[[Category:Sympatholytic drugs]]
   
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Latest revision as of 06:57, November 18, 2008

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Reserpine
Reserpine

methyl-11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl)

oxy]-3β,20α-yohimban-16β-carboxylate[2]
IUPAC name

CAS number
50-55-5
ATC code

C02AA02

PubChem
5770
DrugBank
APRD00472
Chemical formula {{{chemical_formula}}}
Molecular weight 608.68 g/mol
Bioavailability 50%
Metabolism gut/liver
Elimination half-life phase 1 = 4.5h,</br> phase 2 = 271h, </br> average = 33h
Excretion 62% feces / 8% urine
Pregnancy category D (fetotoxic)
Legal status Rx-only (some countries banned/discontinued)
Routes of administration oral

Reserpine is an indole alkaloid[3] antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic behaviors, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.[1] The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines (among the others) from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance. .[4] Reserpine depletion of monoamine neurotransmitters in the synapses is often cited as evidence to the theory that depletion of the neurotransmitters causes subsequent depression in humans. Moreover, reserpine has a peripheral action in many parts of the body, resulting in a preponderance of the cholinergic part of the nervous system (GI-Tract, smooth muscles vessels).

Mode of actionEdit

Reserpine acts by blocking the vesicular monoamine transporter VMAT, which normally transports free norepinephrine, serotonin, and dopamine from the cytoplasm of the presynaptic nerve into vesicles for subsequent release into the synaptic cleft. The unprotected neurotransmitters are then metabolized by MAO and therefore never reach the synapse. [2]

HistoryEdit

Reserpine was isolated in 1952 from the dried root of Rauwolfia serpentina (Indian snakeroot),[5] (which had been known as Sarpaganda and had been used for centuries there for the treatment of insanity, as well as fever and snakebites[3] — even Mahatma Gandhi used it as a tranquilizer during his lifetime.[4]) and introduced in 1954, two years after chlorpromazine.[6] Reserpine almost irreversibly blocks the uptake (and storage) of norepinephrine (i.e. noradrenaline) and dopamine into synaptic vesicles by inhibiting the Vesicular Monoamine Transporters (VMAT).[7]

Reserpine has been discontinued in the UK for some years due to its vast interactions and side effects.

Reserpine was also highly influential in promoting the thought of a biogenic-amine hypothesis of depression - see Everett & Tolman, 1959.

Uses todayEdit

Reserpine is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality: The Hypertension Detection and Follow-up Program,[5] the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents,[6] and the Systolic Hypertension in the Elderly Program.[7]

Reserpine is listed as a second line choice by the JNC 7.[8] Reserpine is a second-line adjunct agent for patients who are uncontrolled on a diuretic when cost is an issue.[9]

It is also used to treat symptoms of dyskinesia in patients sufferring from Huntington's disease.[10]

In some countries reserpine is still available as part of combination drugs for the treatment of hypertension, in most cases they contain also a diuretic and/or a vasodilator like hydralazine. These combinations are currently regarded as second choice drugs. The daily dose of reserpine in antihypertensive treatment is as low as 0.1 to 0.25mg. The use of reserpine as an antipsychotic drug has been nearly completely abandoned. Originally, doses of 0.5mg to 40mg daily were used to treat psychotic diseases. Doses in excess of 3mg daily often required use of an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism. Reserpine may be used as a sedative for horses.

Side effectsEdit

At doses of less than 0.2 mg/day, reserpine has few side effects, most commonly is nasal congestion.[11]

There has been much concern about reserpine causing depression leading to suicide. However, this was reported in uncontrolled studies using doses averaging 0.5 mg per day.[12][13]

Reserpine can cause: nasal congestion, nausea, vomiting, weight gain, gastric intolerance, gastric ulceration (due to increased cholinergic activity in gastric tissue and impaired mucosal quality), stomach cramps and diarrhea are noted. The drug causes hypotension and bradycardia and may worsen asthma. Congested nose and erectile dysfunction are other consequences of alpha-blockade. Depression can occur at any dose and may be severe enough to lead to suicide. Other central effects are a high incidence of drowsiness, dizziness, and nightmares. Parkinsonism occurs in a dose dependent manner. General weakness or fatigue is quite often encountered. High dose studies in rodents found reserpine to cause fibroadenoma of the breast and malignant tumors of the seminal vesicles among others. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed. Besides, it may also cause hyperprolactinemia.

ReferencesEdit

  1. [1] The Columbia Encyclopedia, Sixth Edition. Copyright © 2001-05 Columbia University Press.
  2. Ellenhorn & Barceloux , 1989; Gilman et al, 1990.
  3. Op. cit. Columbia Encyclopedia
  4. Pills for Mental Illness?, TIME Magazine, November 8, 1954
  5. (1979) Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 242 (23): 2562–71. full text at OVID
  6. (1967) Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 202 (11): 1028–34.
  7. (1991) Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 265 (24): 3255–64.
  8. Chobanian AV, Bakris GL, Black HR, et al (2003). The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289 (19): 2560–72. summary
  9. Moser M (1987). "Cost containment" in the management of hypertension. Ann. Intern. Med. 107 (1): 107–9.
  10. Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics, 11, Minireview.
  11. Curb JD, Schneider K, Taylor JO, Maxwell M, Shulman N (1988). Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program. Hypertension 11 (3 Pt 2): II51–5.
  12. QUETSCH RM, ACHOR RW, LITIN EM, FAUCETT RL (1959). Depressive reactions in hypertensive patients; a comparison of those treated with Rauwolfia and those receiving no specific antihypertensive treatment. Circulation 19 (3): 366–75.
  13. LEMIEUX G, DAVIGNON A, GENEST J (1956). Depressive states during Rauwolfia therapy for arterial hypertension; a report of 30 cases. Canadian Medical Association journal 74 (7): 522–6.

FootnotesEdit

  1. ^  アルカロイド (Alkaloids) (T-Z). 2004.
  2. ^  "Indole Alkaloids" Major Types Of Chemical Compounds In Plants & Animals Part II: Phenolic Compounds, Glycosides & Alkaloids. Wayne's Word: An On-Line Textbook of Natural History. 2005.
  3. ^  Forney, Barbara. Reserpine for Veterinary Use Wedgewood Pharmacy. 2001-2002.
  4. ^  Rauwolfia Dorlands Medical Dictionary. Merck Source. 2002.
  5. ^  Lopez-Munoz F, Bhatara VS, Alamo C, Cuenca E. (2004): "[Historical approach to reserpine discovery and its introduction in psychiatry]" [Article in Spanish] Actas Esp Psiquiatr. 32(6):387-95. PMID 15529229 Fulltext in English and Spanish
  6. ^ Schuldiner, S. et al. (1993): J. Biol. Chem. 268(1) 29-34. PMID 8416935

External links Edit

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