- antihypertensive consisting of an alkaloid extracted from the plant Rauwolfia serpentina (trade names Raudixin or Rau-Sed or Sandril or Serpasil) (同)Raudixin, Rau-Sed, Sandril, Serpasil
|AHFS/Drugs.com||Consumer Drug Information|
|Biological half-life||phase 1 = 4.5h,
phase 2 = 271h,
|Excretion||62% feces / 8% urine|
|Chemical and physical data|
|Molar mass||608.68 g/mol|
|3D model (JSmol)||
Reserpine (also known by trade names Raudixin, Serpalan, Serpasil) 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 symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today. The antihypertensive actions of reserpine are a result of its ability to deplete catecholamines (among other monoamine neurotransmitters) from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral vascular resistance.
Reserpine-mediated depletion of monoamine neurotransmitters in the synapses is often cited as evidence to the theory that depletion of the monoamine neurotransmitters causes subsequent depression in humans (c.f. monoamine hypothesis). However, this claim is not without controversy. The reserpine-induced depression is considered by some researchers to be a myth, while others claim that teas made out of the plant roots containing reserpine have a calming, sedative action that can actually be considered antidepressant. Notably, reserpine was the first compound shown to be an effective antidepressant in a randomized placebo-controlled trial.
Moreover, reserpine has a peripheral action in many parts of the body, resulting in a preponderance of the effects of the cholinergic part of the autonomous nervous system on the GI tract, smooth muscles, blood vessels, etc.
- 1 Mechanism of action
- 2 Biosynthetic pathway
- 3 History
- 4 Uses today
- 4.1 Medical
- 4.2 Veterinary and other
- 5 Side effects
- 6 References
- 7 External links
Mechanism of action
Reserpine irreversibly blocks the vesicular monoamine transporter (VMAT). This normally transports free intracellular norepinephrine, serotonin, and dopamine in the presynaptic nerve terminal into presynaptic vesicles for subsequent release into the synaptic cleft ("exocytosis"). Unprotected neurotransmitters are metabolized by MAO (as well as by COMT) in the cytoplasm and consequently never excite the post-synaptic cell. Thus, reserpine decreases metabolic rate of monoamine neurotransmitters; but also decreases magnitude of monoamine release.
It may take the body days to weeks to replenish the depleted VMAT, so reserpine's effects are long-lasting.
This depletion of dopamine can lead to drug-induced parkinsonism.
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.
Reserpine was isolated in 1952 from the dried root of Rauwolfia serpentina (Indian snakeroot), which had been known as Sarpagandha and had been used for centuries in India for the treatment of insanity, as well as fever and snakebites — Mahatma Gandhi used it as a tranquilizer. It was first used in the United States by Robert Wallace Wilkins in 1950. Its molecular structure was elucidated in 1953 and natural configuration published in 1955. It was introduced in 1954, two years after chlorpromazine. The first total synthesis was accomplished by R. B. Woodward in 1958.
Reserpine almost irreversibly blocks the uptake (and storage) of norepinephrine (i.e. noradrenaline) and dopamine into synaptic vesicles by inhibiting the vesicular monoamine transporter 2 (VMAT2).
Reserpine has been discontinued in the UK for some years due to its numerous interactions and side effects.
Reserpine was also highly influential in promoting the thought of a biogenic amine hypothesis of depression — see Everett & Tolman, 1959.
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, the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents, and the Systolic Hypertension in the Elderly Program.. However, these studies are dated, with the results of the most recent study being published in 1991.
Reserpine is rarely used in the management of hypertension today. Reserpine is listed as an option by the JNC 7. In 1987, Reserpine was considered a second-line adjunct agent for patients who were uncontrolled on a diuretic alone when cost was an issue.. However, there are far safer generic first/second-line medications available today that can be combined with diuretics, notably the ACE inhibitors and the angiotensin II receptor antagonists.
It was previously used to treat symptoms of dyskinesia in patients suffering from Huntington's disease., but alternative medications are preferred 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 antihypertensive treatment is as low as 0.1 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.
Veterinary and other
Reserpine may be used as a sedative for horses.
Another frequent use of reserpine is in the field of mass spectrometry where it is widely used as a reference standard owing to its availability, ease of ionization under electrospray conditions and stability in solution.
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.
Reserpine is no longer available in the United Kingdom; however it is still available in the United States
At doses of less than 0.2 mg/day, reserpine has few side effects, the most common of which is nasal congestion.
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.
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. It may also cause hyperprolactinemia.
Reserpine passes into breast milk and is harmful to breast-fed infants, and should therefore be avoided during breastfeeding if possible.
It also produces a dangerous decline in blood pressure at doses needed for treatment.
- "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.
-  The Columbia Encyclopedia, Sixth Edition. Copyright © 2001-05 Columbia University Press.
- Forney, Barbara. Reserpine for Veterinary Use Wedgewood Pharmacy. 2001-2002.
- Baumeister, A. A.; Hawkins, M. F.; Uzelac, S. M. (2003). "The Myth of Reserpine-Induced Depression: Role in the Historical Development of the Monoamine Hypothesis". Journal of the History of the Neurosciences. 12 (2): 207–220. PMID 12953623. doi:10.1076/jhin.220.127.116.1135.
- Davies D. L.; Shepherd M. (1955). "Reserpine in the Treatment of Anxious and Depressed Patients". The Lancet. 269: 117–20. doi:10.1016/s0140-6736(55)92118-8.
- Henry, J.; Scherman, D. (1989). "Radioligands of the vesicular monoamine transporter and their use as markers of monoamine storage vesicles". Biochemical Pharmacology. 38 (15): 2395–2404. PMID 2667522. doi:10.1016/0006-2952(89)90082-8.
- Eiden, LE; Weihe, E (2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. PMC . PMID 21272013. doi:10.1111/j.1749-6632.2010.05906.x.
- Barcelos, R. C. S.; Benvegnú, D. M.; Boufleur, N.; Pase, C.; Teixeira, A. L. M.; Reckziegel, P. C.; Emanuelli, T.; Da Rocha, J. O. B. T.; Bürger, M. E. (2010). "Short Term Dietary Fish Oil Supplementation Improves Motor Deficiencies Related to Reserpine-Induced Parkinsonism in Rats". Lipids. 46 (2): 143–149. PMID 21161603. doi:10.1007/s11745-010-3514-0.
- Ramawat et al, 1999.Ramawat KG; Rachnana Sharma; Suri SS. Ramawat, KG.; Merillon, JM., eds. Medicinal Plants in Biotechnology- Secondary metabolites 2nd edition 2007. Oxford and IBH, India. pp. 66–367. ISBN 978-1-57808-428-9.
- Rauwolfia Dorlands Medical Dictionary. Merck Source. 2002.
- Pills for Mental Illness?, TIME Magazine, November 8, 1954
- Nicolaou, K. C.; E. J. Sorensen (1996). Classics in Total Synthesis. Weinheim, Germany: VCH. p. 55. ISBN 3-527-29284-5.
- López-Muñoz F, Bhatara VS, Alamo C, Cuenca E (2004). "[Historical approach to reserpine discovery and its introduction in psychiatry]". Actas Esp Psiquiatr. 32: 387–95. PMID 15529229.
- Schuldiner S.; et al. (1993). "Reserpine binding to a vesicular amine transporter expressed in Chinese hamster ovary fibroblasts". J. Biol. Chem. 268 (1): 29–34. PMID 8416935.
- , (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. PMID 490882. doi:10.1001/jama.242.23.2562. full text at OVID
- , (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. PMID 4862069. doi:10.1001/jama.202.11.1028.
- , (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. PMID 2046107. doi:10.1001/jama.265.24.3255.
- Shamon SD, Perez MI (2009). "Blood pressure lowering efficacy of reserpine for primary hypertension". Cochrane Database of Systematic Reviews. 4: CD007655. PMID 19821434. doi:10.1002/14651858.CD007655.pub2.
- 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. PMID 12748199. doi:10.1001/jama.289.19.2560. summary
- Moser M (1987). ""Cost containment" in the management of hypertension". Ann. Intern. Med. 107 (1): 107–9. PMID 3592424. doi:10.7326/0003-4819-107-1-107.
- Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 11. ISBN 1-59541-101-1.
- Bhomraj Thanvi, Nelson Lo, and Tom Robinson: Levodopa‐induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment.Postgrad Med J. 2007 Jun; 83(980): 384–388. PMCID: PMC2600052. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600052/
- Forney B. Reserpine for veterinary use. Available at http://www.wedgewoodpetrx.com/learning-center/professional-monographs/reserpine-for-veterinary-use.html.
- 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. PMID 3350594. doi:10.1161/01.hyp.11.3_pt_2.ii51.
- 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. PMID 13629798. doi:10.1161/01.cir.19.3.366.
- 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. PMC . PMID 13304797.
- AJ Giannini, HR Black. Psychiatric, Psychogenic, and Somatopsychic Disorders Handbook. Garden City, NY. Medical Examination Publishing, 1978. Pg. 233. ISBN 0-87488-596-5.
- kidsgrowth.org --> Drugs and Other Substances in Breast Milk Retrieved on June 19, 2009
- Pinel, John P.J. (2011). Biopsychology (8th ed.). Boston: Allyn & Bacon. p. 469. ISBN 978-0205832569.
- NLM Hazardous Substances Databank – Reserpine
- PubChem Substance Summary: Reserpine National Center for Biotechnology Information.
- The Stork Synthesis of (−)-Reserpine
Sympatholytic (and closely related) antihypertensives (C02)
Monoamine reuptake inhibitors
See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins
Xenobiotic-sensing receptor modulators
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. 初期治療に抵抗性を示したレイノー現象の治療 treatment of the raynaud phenomenon resistant to initial therapy
- 2. 高齢者における高血圧、特に収縮期高血圧の治療 treatment of hypertension in the elderly patient particularly isolated systolic hypertension
- 3. 遅発性ジスキネジア：予防および治療 tardive dyskinesia prevention and treatment
- 4. 高プロラクチン血症の原因 causes of hyperprolactinemia
- 5. 成人における複合性局所疼痛症候群の予防およびマネージメント prevention and management of complex regional pain syndrome in adults
- Common Variants in TGFBR2 and miR-518 Genes Are Associated With Hypertension in the Chinese Population.
- Chen J1, Zhao X2, Wang H3, Chen Y2, Wang W2, Zhou W2, Wang X4, Tang J4, Zhao Y5, Lu X6, Chen S6, Wang L7, Shen C8, Yang S2.
- American journal of hypertension.Am J Hypertens.2014 Oct;27(10):1268-76. doi: 10.1093/ajh/hpu047. Epub 2014 Mar 31.
- BACKGROUND: An animal study reported that TGF-β1 maturation was linked to the homeostasis of blood pressure and elastogenesis of essential hypertension (EH). Recent advances require further research of TGF-β1 receptor in EH.METHODS: A case-control study comprised of 2,012 adult hypertension case p
- PMID 24687999
- Preventive effect of insect tea against reserpine-induced gastric ulcers in mice.
- Zhou YL, Wang R, Feng X, Zhao X.
- Experimental and therapeutic medicine.Exp Ther Med.2014 Oct;8(4):1318-1324. Epub 2014 Jul 23.
- The aim of the present study was to determine the preventive effect of insect tea against reserpine-induced gastric ulcers in ICR mice. A high (800 mg/kg) dose of insect tea reduced the serum levels of the proinflammatory cytokines interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interf
- PMID 25187847
- Gravitational sampling electrospray ionization mass spectrometry for real-time reaction monitoring.
- Hsu FJ1, Liu TL, Laskar AH, Shiea J, Huang MZ.
- Rapid communications in mass spectrometry : RCM.Rapid Commun Mass Spectrom.2014 Sep 30;28(18):1979-86. doi: 10.1002/rcm.6989.
- RATIONALE: The elucidation of chemical reaction mechanisms has attracted tremendous interest in recent years. Here, gravitational sampling electrospray ionization mass spectrometry (GS-ESI-MS) is used to explore a simple method for the real-time monitoring of chemical and biochemical reactions.METHO
- PMID 25132298
- Norepinephrine Enhances Radiosensitivity in Rat Ileal Epithelial Cells
- MATSUU MATSUYAMA Mutsumi,OKAICHI Kumio,SHICHIJO Kazuko,NAKAYAMA Toshiyuki,NAKASHIMA Masahiro,SEKINE Ichiro
- Journal of radiation research 52(3), 369-373, 2011-05-16
- … Moreover, these same cells showed a suppression of apoptosis when reserpine was administered to induce sympathetic dysfunction in spontaneously hypertensive rats or Wistar-Kyoto rats.1) Whether the hyperfunction of the sympathetic nervous system is involved in the high susceptibility of the jejunal crypt cells to radiation-induced apoptosis was the subject of this study. …
- NAID 10028111495
- 注射薬 pazufloxacin 1 回1,000mg 1日2回投与時の細菌性肺炎を対象とした臨床第III相試験
- 河野 茂,青木 信樹,河合 伸,二木 芳人,渡辺 彰,堀 誠治,渡辺 晋一,戸塚 恭一
- 日本化学療法学会雜誌 = Japanese journal of chemotherapy 58(6), 664-680, 2010-11-10
- … 2）PZFX 500 mg×2回/日投与時の24時間後の菌液では，薬剤非添加時に比べ感受性が1/2に低下したポピュレーションが一部認められたが，GyrA, GyrB, ParCおよびParEのキノロン耐性決定領域（quinolone resistance-determining region：QRDR）にアミノ酸変異はなく，reserpine添加により影響を受ける薬剤排出ポンプの発現亢進は認められなかった。 …
- NAID 10027469199
- reserpine re·ser·pine (rĭ-sûr'pēn', -pĭn, rěs'ər-pĭn, -pēn', rěz'-) n. A white to yellowish powder isolated from the roots of certain species of Asian shrubs and used as a sedative and an antihypertensive. The American Heritage ...
- Reserpine official prescribing information for healthcare professionals. Includes: indications, dosage, adverse reactions, pharmacology and more. ... Warnings Extreme caution should be exercised in treating patients with a history of ...