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Peripheral effects of fenfluramine

G E Mitchell, D R Mottram

British Journal of Pharmacology

|June 1, 1976

Summary

This summary is machine-generated.

Fenfluramine hydrochloride, an appetite suppressant, causes prolonged hypotension in rats by affecting adrenergic nerve terminals. This mechanism involves either displacing noradrenaline or inhibiting amine uptake, impacting cardiovascular responses.

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Area of Science:

Pharmacology
Cardiovascular Physiology
Neuroscience

Background:

Fenfluramine hydrochloride is a centrally acting anorexigenic agent.
Its peripheral cardiovascular effects require detailed investigation.

Purpose of the Study:

To investigate the peripheral cardiovascular effects of fenfluramine hydrochloride in rats.
To elucidate the mechanism underlying fenfluramine's hypotensive action.

Main Methods:

Intravenous administration of fenfluramine hydrochloride in rats.
Measurement of blood pressure responses to fenfluramine and sympathomimetic amines (tyramine, methoxamine, metaraminol).
Studies on isolated rat vas deferens.
Use of antagonists like propranolol, atropine, phentolamine, and thymoxamine.

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Main Results:

Fenfluramine induced immediate hypotension followed by a prolonged fall in blood pressure.
Responses to indirectly acting tyramine were significantly reduced (50%) by fenfluramine, while direct sympathomimetics were unaffected.
Fenfluramine caused spontaneous vas deferens contractions, blocked by alpha-adrenoceptor antagonists.

Conclusions:

Fenfluramine hydrochloride exerts peripheral cardiovascular effects, primarily hypotension.
The drug appears to act at the adrenergic nerve terminal, likely by displacing noradrenaline or inhibiting amine uptake.
These findings suggest a novel mechanism for fenfluramine's anorexigenic and cardiovascular actions.