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| {{Drugbox|
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| |IUPAC_name = ''methyl-11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl)<br>
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| ''oxy]-3β,20α-yohimban-16β-carboxylate''{{ref|iupac}}
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| | image=Reserpine.png
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| | CAS_number=50-55-5
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| | ATC_prefix=C02
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| | ATC_suffix=AA02
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| | PubChem=5770
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| | DrugBank=APRD00472
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| | C=33 | H=40 | N=2 | O=9
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| | molecular_weight = 608.68 g/mol
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| | bioavailability= 50%
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| | metabolism = gut/liver
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| | elimination_half-life=phase 1 = 4.5h,</br> phase 2 = 271h, </br> average = 33h
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| | excretion = 62% feces / 8% urine
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| | pregnancy_category = D (fetotoxic)
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| | legal_status = Rx-only (some countries banned/discontinued)
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| | licence_US = Reserpine
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| | routes_of_administration= oral
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| }}
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| {{CMG}}
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| __NOTOC__ | | __NOTOC__ |
| | {{Reserpine}} |
| | {{CMG}}; {{AE}} |
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| | '''''For patient information about Reserpine, click [[Reserpine (patient information)|here]].''''' |
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| ==[[Reserpine (patient information)|For patient information, click here]]==
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| ==Overview== | | ==Overview== |
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| '''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 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. .{{ref|veterinary1}} Reserpine depletion of monoamine neurotransmitters in the synapses 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). | | '''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 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. .{{ref|veterinary1}} Reserpine depletion of monoamine neurotransmitters in the synapses 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). |
| | ==Category== |
| | Central [[alpha blockers]]. |
| | ==FDA Package Insert== |
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| ==Mode of action== | | ====RESERPINE<sup>®</sup>==== |
| Reserpine acts via disruption of norepinepherine, serotonin, and dopamine presynaptic vesicles by the transporter [[VMAT]]. The neurotransmitters are subsequently metabolized by MAO and therefore never reach the synapse.
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| ==History==
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| 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>) and introduced it 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}}
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| Reserpine has been discontinued in the UK for some years due to its vast interactions and side effects. | | ''' [[Reserpine indications and usage|Indications and Usage]]''' |
| | '''| [[Reserpine dosage and administration|Dosage and Administration]]''' |
| | '''| [[Reserpine dosage forms and strengths|Dosage Forms and Strengths]]''' |
| | '''| [[Reserpine contraindications|Contraindications]]''' |
| | '''| [[Reserpine warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Reserpine adverse reactions|Adverse Reactions]]''' |
| | '''| [[Reserpine drug interactions|Drug Interactions]]''' |
| | '''| [[Reserpine use in specific populations|Use in Specific Populations]]''' |
| | '''| [[Reserpine overdosage|Overdosage]]''' |
| | '''| [[Reserpine description|Description]]''' |
| | '''| [[Reserpine clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Reserpine nonclinical toxicology|Nonclinical Toxicology]]''' |
| | '''| [[Reserpine clinical studies|Clinical Studies]]''' |
| | '''| [[Reserpine how supplied storage and handling|How Supplied/Storage and Handling]]''' |
| | '''| [[Reserpine patient counseling information|Patient Counseling Information]]''' |
| | '''| [[Reserpine labels and packages|Labels and Packages]]''' |
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| Reserpine was also highly influential in promoting the thought of a biogenic-amine hypothesis of depression - see Everett & Tolman, 1959.
| | ==Mechanism of Action== |
| | | Reserpine acts via disruption of norepinepherine, serotonin, and dopamine presynaptic vesicles by the transporter [[VMAT]]. The neurotransmitters are subsequently metabolized by MAO and therefore never reach the synapse. |
| ==Uses today== | | ==References== |
| 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 n 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> | |
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| 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 an excellent second agent for patients who are uncontrolled on a diuretic.<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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| 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.
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| ==Side effects== | |
| 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>
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| 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>
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| 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 semen vesicles among others. Early suggestions that reserpine causes breast cancer in women (risk approximately doubled) were not confirmed. Besides, it may also cause hyperprolactinemia.
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| ==References==
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| {{Reflist|2}} | | {{Reflist|2}} |
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| ==Additional Resources==
| | [[Category:Cardiovascular Drugs]] |
| # {{note|iupac}} [http://homepage1.nifty.com/nomenclator/triv/alka_t-z.htm アルカロイド (Alkaloids) (T-Z)]. 2004.
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| # {{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.
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| # {{note|veterinary1}} Forney, Barbara. [http://www.wedgewoodpharmacy.com/monographs/reserpine.asp Reserpine for Veterinary Use] Wedgewood Pharmacy. 2001-2002.
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| # {{note|mercksource}} [http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_r_03zPzhtm#1093125 Rauwolfia] Dorlands Medical Dictionary. Merck Source. 2002.
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| # {{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]
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| # {{note|VMAT}}Schuldiner, S. et al. (1993): ''J. Biol. Chem.'' 268(1) 29-34. PMID 8416935
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| == External links ==
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| *[http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+50-55-5 NLM Hazardous Substances Databank – Reserpine]
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| *[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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| *[http://www.organic-chemistry.org/Highlights/2006/01May.shtm The Stork Synthesis of (-)-Reserpine]
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| {{Antihypertensives and diuretics}}
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| [[Category:Indole alkaloids]]
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| [[Category:VMAT inhibitors]]
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| [[Category:Antihypertensive agents]] | |
| [[Category:Drugs]] | | [[Category:Drugs]] |
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