Reserpine
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Trade names | Serpasil, others |
AHFS/Drugs.com | Consumer Drug Information |
MedlinePlus | a601107 |
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Routes of administration | Oral |
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Pharmacokinetic data | |
Bioavailability | 50% |
Metabolism | gut/liver |
Elimination half-life | phase 1 = 4.5h, phase 2 = 271h, average = 33h |
Excretion | 62% feces / 8% urine |
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Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator.[1] Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955,[2] the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone.[3][4][5] The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available In 2012.[6]
The antihypertensive actions of reserpine are largely due to its antinoradrenergic effects, which are a result of its ability to deplete
At doses of 0.05 to 0.2 mg per day, reserpine is well tolerated;[8] the most common adverse effect being nasal stuffiness.
Reserpine has also been used for relief of
Medical uses
Reserpine is recommended as an alternative drug for treating hypertension by the JNC 8.
It was previously used to treat symptoms of dyskinesia in patients with Huntington's disease,[17] but alternative medications are preferred today.[18]
The daily dose of reserpine in antihypertensive treatment is as low as 0.05 to 0.25 mg. The use of reserpine as an antipsychotic drug had been nearly completely abandoned, but more recently it made a comeback as adjunctive treatment, in combination with other antipsychotics, so that more refractory patients get dopamine blockade from the other antipsychotic, and dopamine depletion from reserpine. Doses for this kind of adjunctive goal can be kept low, resulting in better tolerability. Originally, doses of 0.5 mg to 40 mg daily were used to treat psychotic diseases.
Doses in excess of 3 mg daily often required use of an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism. For adjunctive treatment, doses are typically kept at or below 0.25 mg twice a day.
Adverse effects
At doses of less than 0.2 mg/day, reserpine has few adverse effects, the most common of which is nasal congestion.[19]
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. The drug causes hypotension and bradycardia and may worsen asthma. Congested nose and erectile dysfunction are other consequences of alpha-blockade.[20]
Central nervous system effects at higher doses (0.5 mg or higher) include drowsiness, dizziness, nightmares, Parkinsonism, general weakness and fatigue. [21]
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. It may also cause
Reserpine passes into breast milk and is harmful to breast-fed infants, and should therefore be avoided during breastfeeding if possible.[22]
It may produce an excessive decline in blood pressure at doses needed for treatment of anxiety, depression, or psychosis.[23]
Mechanism of action
Reserpine irreversibly blocks the H+-coupled
Biosynthetic pathway
Reserpine is one of dozens of indole alkaloids isolated from the plant Rauvolfia serpentina.[27] In the Rauvolfia plant, tryptophan is the starting material in the biosynthetic pathway of reserpine, and is converted to tryptamine by tryptophan decarboxylase enzyme. Tryptamine is combined with secologanin in the presence of strictosidine synthetase enzyme and yields strictosidine. Various enzymatic conversion reactions lead to the synthesis of reserpine from strictosidine.[28]
History
Reserpine was isolated in 1952 from the dried root of
Reserpine was influential in promoting the thought of a
Research
Antibacterial effects
Reserpine inhibits formation of biofilms by Staphylococcus aureus and inhibits the metabolic activity of bacteria present in biofilms.[40]
Veterinary
Reserpine is used as a long-acting tranquilizer to subdue excitable or difficult horses and has been used illicitly for the sedation of show horses, for-sale horses, and in other circumstances where a "quieter" horse might be desired.[41]
It is also used in dart guns.
References
- S2CID 32904492.
- ^ "Reserpine".
- PMID 24352797.
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- ^ Forney, Barbara. Reserpine for Veterinary Use Wedgewood Pharmacy. 2001-2002.
- S2CID 207489850.
- PMID 29373456.
- PMID 27124109.
- PMID 24352797.
- PMID 27997978.
- PMID 490882. full text at OVID
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- PMID 2046107.
- from the original on November 26, 2009.
- ISBN 978-1-59541-101-3.
- PMID 17551069.
- PMID 3350594.
- ^ ISBN 0-87488-596-5.
- S2CID 4036935.
- ^ kidsgrowth.org Drugs and Other Substances in Breast Milk Archived 2007-06-23 at archive.today Retrieved on June 19, 2009
- ISBN 978-0-205-83256-9.
- PMID 29666153.
- PMID 21272013.
- PMID 26408528.
- ^ "Indole Alkaloids" Archived 2011-09-02 at the Wayback Machine 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.
- ISBN 978-1-57808-428-9.
- ^ Rauwolfia Dorlands Medical Dictionary. Merck Source. 2002.
- ^ "Reserpine". The Columbia Encyclopedia (Sixth ed.). Columbia University Press. 2005. Archived from the original on 2009-02-12.
- TIME Magazine, November 8, 1954
- ^ ISBN 978-3-527-29284-4.
- PMID 15529229.
- ^ Everett GM, Toman JE (1959). "Mode of action of Rauwolfia alkaloids and motor activity". Biol Psychiat. 2: 75–81.
- ISBN 978-981-334-140-1.
- S2CID 42407412.
- PMID 14392947.
- ISBN 978-0-674-03958-2.
- ^ S2CID 251765916.
- PMID 31605761.
- ^ Forney B. Reserpine for veterinary use. Available at http://www.wedgewoodpetrx.com/learning-center/professional-monographs/reserpine-for-veterinary-use.html.
External links
- NLM Hazardous Substances Databank – Reserpine
- PubChem Substance Summary: Reserpine National Center for Biotechnology Information.
- The Stork Synthesis of (−)-Reserpine