Reserpine

Source: Wikipedia, the free encyclopedia.
Reserpine
resperine 2D skeletal
resperine 3D BS
Clinical data
Trade namesSerpasil, others
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa601107
License data
Pregnancy
category
  • C
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • Rx-only (banned/discontinued in some countries)
Pharmacokinetic data
Bioavailability50%
Metabolismgut/liver
Elimination half-lifephase 1 = 4.5h,
phase 2 = 271h,
average = 33h
Excretion62% feces / 8% urine
Identifiers
  • methyl (3β,16β,17α,18β,20α)-11,17-dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylate and
JSmol)
  • [H][C@]26C[C@@H](OC(=O)c1cc(OC)c(OC)c(OC)c1)[C@H](OC)[C@@H](C(=O)OC)[C@@]2([H])C[C@]5([H])c4[nH]c3cc(OC)ccc3c4CCN5C6
  • InChI=1S/C33H40N2O9/c1-38-19-7-8-20-21-9-10-35-16-18-13-27(44-32(36)17-11-25(39-2)30(41-4)26(12-17)40-3)31(42-5)28(33(37)43-6)22(18)15-24(35)29(21)34-23(20)14-19/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3/t18-,22+,24-,27-,28+,31+/m1/s1 checkY
  • Key:QEVHRUUCFGRFIF-MDEJGZGSSA-N checkY
  (verify)

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

monoamine neurotransmitters) from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral vascular resistance.[7]

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

psychotic symptoms.[9] A review found that in persons with schizophrenia, reserpine and chlorpromazine had similar rates of adverse effects, but that reserpine was less effective than chlorpromazine for improving a person's global state.[10]

Medical uses

Reserpine is recommended as an alternative drug for treating hypertension by the JNC 8.

randomized controlled trials: The Hypertension Detection and Follow-up Program,[13] the Veterans Administration Cooperative Study Group in Anti-hypertensive Agents,[14] and the Systolic Hypertension in the Elderly Program.[15] Moreover, reserpine was included as a secondary antihypertensive option for patients who did not achieve blood pressure lowering targets in the ALLHAT study.[16]

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

hyperprolactinemia.[20]

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

COMT), attached to the outer membrane of the mitochondria in the cytosol of the axon terminals, and consequently never excite the post-synaptic cell. Thus, reserpine increases removal of monoamine neurotransmitters from neurons, decreasing the size of the neurotransmitter pools, and thereby decreasing the amplitude of neurotransmitter release.[25] As it may take the body days to weeks to replenish the depleted VMATs, reserpine's effects are long-lasting.[26]

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

R. B. Woodward in 1958.[32]

Reserpine was influential in promoting the thought of a

quality of evidence was limited, and only a subset of studies were randomized controlled trials.[39]

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

  1. S2CID 32904492
    .
  2. ^ "Reserpine".
  3. PMID 24352797
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  4. .
  5. .
  6. .
  7. ^ Forney, Barbara. Reserpine for Veterinary Use Wedgewood Pharmacy. 2001-2002.
  8. S2CID 207489850
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  9. .
  10. .
  11. .
  12. .
  13. .
  14. .
  15. from the original on November 26, 2009.
  16. .
  17. .
  18. .
  19. ^ .
  20. .
  21. ^ kidsgrowth.org Drugs and Other Substances in Breast Milk Archived 2007-06-23 at archive.today Retrieved on June 19, 2009
  22. .
  23. .
  24. .
  25. .
  26. ^ "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.
  27. .
  28. ^ Rauwolfia Dorlands Medical Dictionary. Merck Source. 2002.
  29. ^ "Reserpine". The Columbia Encyclopedia (Sixth ed.). Columbia University Press. 2005. Archived from the original on 2009-02-12.
  30. TIME Magazine
    , November 8, 1954
  31. ^ .
  32. .
  33. ^ Everett GM, Toman JE (1959). "Mode of action of Rauwolfia alkaloids and motor activity". Biol Psychiat. 2: 75–81.
  34. .
  35. .
  36. .
  37. .
  38. ^ .
  39. .
  40. ^ Forney B. Reserpine for veterinary use. Available at http://www.wedgewoodpetrx.com/learning-center/professional-monographs/reserpine-for-veterinary-use.html.

External links