PERIPHERAL EFFECTS OF FENFLURAMINE

• Published in: British journal of pharmacology Vol. 57; no. 2; pp. 185 - 189
• Main Authors: MITCHELL, G.E.D., MOTTRAM, D.R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.1976
• Subjects: Amines - pharmacology; Animals; Blood Pressure - drug effects; Drug Interactions; Female; Fenfluramine - pharmacology; In Vitro Techniques; Male; Rats; Sympathetic Nervous System - drug effects; Sympathomimetics - pharmacology; Tyramine - pharmacology; Vas Deferens - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1976.tb07466.x

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.