The Sympathomimetic Activity of Fenfluramine Hydrochloride on Rat Vas Deferens

Abstract

The peripheral, pharmacological effects of the anorexigenic agent, fenfluramine hydrochloride, have been investigated on rat isolated vas deferens. Characteristic spiked contractions were observed within 2 to 3 min after exposure to fenfluramine; these contractions reached a rate of around 13 per min and were of variable height. Pre‐treatment of vasa with the indirectly acting sympathomimetic amine, tyramine, greatly reduced both the height and rate of contraction induced by fenfluramine. The uptake inhibitor, desipramine, required a concentration in excess of 10 μM to affect fenfluramine‐induced contractions. Effects of desipramine on fenfluramine contractions were of equal magnitude whether desipramine was administered before fenfluramine or at the height of the fenfluramine‐induced contractions. Pre‐treatment with debrisoquine (0.5 mM), reduced the contractions in response to fenfluramine over a period of time. Fenfluramine, added to vasa from rats which had been injected intraperitoneally with 5 mg/kg reserpine 24 h and 48 h previously, failed to induce its characteristic contractions. It is concluded that fenfluramine can be classed as an indirectly acting sympathomimetic amine on peripheral adrenergic nerve terminals.

Calcium modulatory properties of 2,6‐dibutylbenzylamine (B25) in rat isolated vas deferens, cardiac and smooth muscle preparations

“…For example, characteristic rhythmic contractions superimposed on phasic and tonic components have been observed following the exposure of both epididymal and prostatic portions of rat vas deferens to noradrenaline (Ashoori & Tomita, 1983). A similar phenomenon has also been observed in the whole vas deferens with fenfluramine, methoxamine, 5hydroxytryptamine, kassinin, KCI and BaCl2 (Mottram & Wadhwani, 1977;Hay & Wadsworth, 1979;Hay & Wadsworth, 1983;Maggi et al, 1987;Mishra et al, 1988).…”

Iris Adrenergic Impairment in Idiopathic Headache

“…Fenfluramine is capable of inducing headache in migraineurs. 19 This drug modifies brain 5-HT turnover 20 ; peripherally it exhibits indirect sympathomimetic properties 21,22 and induces mydriasis. 23,24 Its mydriatic response is predicted by the presence of sympathetic neurons in the iris, with intact stores of NA.…”