Reserpine
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| Reserpine
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| Systematic (IUPAC) name | |
| methyl-11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl) oxy]-3β,20α-yohimban-16β-carboxylate | |
| Identifiers | |
| CAS number | |
| ATC code | C02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C33H40N2O9 |
| Mol. mass | 608.68 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 50% |
| Metabolism | gut/liver |
| Half life | phase 1 = 4.5h, phase 2 = 271h, average = 33h |
| Excretion | 62% feces / 8% urine |
| Therapeutic considerations | |
| Licence data |
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| Pregnancy cat. |
D (fetotoxic) |
| Legal status |
Rx-only (some countries banned/discontinued) |
| Routes | oral |
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Overview
Reserpine is an indole alkaloid 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. . 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 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.
History
Reserpine was isolated in 1952 from the dried root of Rauwolfia serpentina (Indian snakeroot), (which had been known as Sarpaganda and had been used for centuries there for the treatment of insanity, as well as fever and snakebites[1]) and introduced it in 1954, two years after chlorpromazine. 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).
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
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,[1] the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents,[1] and the Systolic Hypertension n the Elderly Program.[1]
Reserpine is listed as a second line choice by the JNC 7.[1] Reserpine is an excellent second agent for patients who are uncontrolled on a diuretic.[1]
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
At doses of less than 0.2 mg/day, reserpine has few side effects, most commonly is nasal congestion.[1]
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.[1][1]
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.
References
Additional Resources
- ^ アルカロイド (Alkaloids) (T-Z). 2004.
- ^ "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.
- ^ Forney, Barbara. Reserpine for Veterinary Use Wedgewood Pharmacy. 2001-2002.
- ^ Rauwolfia Dorlands Medical Dictionary. Merck Source. 2002.
- ^ 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
- ^ Schuldiner, S. et al. (1993): J. Biol. Chem. 268(1) 29-34. PMID 8416935
External links
- NLM Hazardous Substances Databank – Reserpine
- PubChem Substance Summary: Reserpine National Center for Biotechnology Information.
- The Stork Synthesis of (-)-Reserpine
fr:Réserpine hr:Rezerpinsk:Rezerpín
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
