PERIPHERAL EFFECTS OF FENFLURAMINE

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Abstract
1 The peripheral cardiovascular effects of the centrally acting anorexigenic agent, fenfluramine hydrochloride, have been investigated in the rat. 2 After intravenous administration of fenfluramine, an immediate hypotensive response, followed by a reflex rise in blood pressure was recorded. This was followed by a prolonged fall in blood pressure which frequently failed to return to pre-drug levels. 3 The antagonists, propranolol and atropine, failed to inhibit this hypotensive effect of fenfluramine. 4 The effects of 5 mg/kg fenfluramine for 1 h on the blood pressure responses to the sympathomimetic amines, tyramine, methoxamine and metaraminol were studied. 5 The responses to the indirectly acting tyramine were reduced by 50% following fenfluramine, while those to the directly acting methoxamine remained unaffected by the drug. Responses to metaraminol, an amine with both direct and indirect actions, were also unaffected to a significant degree by fenfluramine. 6 Studies on rat isolated vas deferens again showed that responses to tyramine are greatly reduced following fenfluramine. 7 In addition fenfluramine itself produced spontaneous contractions of the vas deferens. These contractions were blocked by the α-adrenoceptor blocking agents phentolamine and thymoxamine. 8 It is suggested that fenfluramine exerts an effect at the adrenergic nerve terminal, either by displacing noradrenaline stores or by inhibition of the amine uptake process.