Article: Reserpine

Reserpine
Systematic (IUPAC) name
methyl-11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl) oxy]-3β,20α-yohimban-16β-carboxylate[1]
Identifiers
CAS number	50-55-5
ATC code	C02AA02
PubChem	5770
DrugBank	APRD00472
Chemical data
Formula	C33H40N2O9
Mol. weight	608.679 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
Pregnancy cat.	D (fetotoxic)
Legal status	Rx-only (some countries banned/discontinued)
Routes	oral

Reserpine is an indole alkaloid^[2] antipsychotic and antihypertensive drug known to irreversibly bind to storage vesicles of neurotransmitters such as dopamine, norepinephrine, and serotonin.^[3] Reserpine depletion of monoamine neurotransmitters in the synapses is often used to bolster the theory that depletion of the neurotransmitters causes subsequent depression in humans. However a 1950's drug trial at Maudsley Hospital found that in fact reserpine, far from causing depression, actually acted as an antidepressant. 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).

History

Reserpine was isolated in 1952 from the dried root of Rauwolfia serpentina (Indian snakeroot),^[4] and introduced in 1954, two years after chlorpromazine.^[5] Reserpine almost irreversibly blocks the accumulation of noradrenaline and dopamine into synaptic vesicles by inhibiting the Vesicular Monoamine Transporters (VMAT).^[6]

Reserpine has been discontinued in the UK for some years due to its vast interactions and side effects.

Uses 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 0.25mg. 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

Reserpine has a high index and severity of side-effects. Often nausea, vomiting, gastric intolerance, gastric ulceration (due to increased cholinergic activity in gastric tissue and impaired mucosal quality), stomach cramps and diarrhea are noted. Otherwise, weight gain can been seen. The drug causes hypotension and bradycardia and may worsen asthma. Congested nose is another consequence of alpha-blockade. Depression does occur 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.