Some 5-hydroxytryptamine-like actions of fenfluramine: a comparison with (+)-amphetamine and diethylpropion.

Abstract

Abstract The 5-hydroxytryptamine (5-HT)-like effects of fenfluramine have been investigated in mice in two different experiments. In a behavioural test in mice pretreated with tranylcypromine, fenfluramine caused stereotyped changes which were similar to those produced by 5-hydroxytryptophan (5-HTP) and were antagonized by methysergide or pretreatment with p-chlorophenylalanine (PCPA). Like 5-HTP, fenfluramine reduced the conditioned response in a one-trial conditioning test, an effect antagonized by methysergide or by PCPA pretreatment. The reduction in the conditioned response caused by a maximal electroconvulsion was also antagonized by PCPA, an effect prevented by 5-HTP. Equivalent anorectic doses of (+)-amphetamine and diethylpropion caused a small increase in stereotyped behaviour, but this was not modified by methysergide; both anorectic drugs were inactive in the one-trial conditioning test. It seems probable that the observed actions of fenfluramine are caused indirectly through the release of endogenous brain 5-HT.