The substituted amphetamines 3,4-methylenedioxymethamphetamine, methamphetamine, p-chloroamphetamine and fenfluramine induce 5-hydroxytryptamine release via a common mechanism blocked by fluoxetine and cocaine
European Journal of Pharmacology – May 01, 1992
Source: OpenAlex
Summary
Fenfluramine and p-chloroamphetamine (PCA) are remarkably effective at inducing serotonin release, surpassing MDMA and methamphetamine in potency. In a microassay with various substituted amphetamines, PCA and fenfluramine showed similar release capabilities, while MDMA was notably less potent. Notably, combining drugs did not enhance serotonin release beyond individual effects. Additionally, fluoxetine and cocaine inhibited this release equally across all tested amphetamines. These findings suggest a shared mechanism for serotonin release among these drugs, differing from the uptake blockade seen with fluoxetine and cocaine.
Abstract
The abilities of the substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, p-chloroamphetamine (PCA) and fenfluramine to induce synaptosomal [3H]serotonin (5-HT) release were compared using a novel microassay system. The rank order of release potencies was found to be (+/-)PCA congruent to (+)-fenfluramine greater than (+)-MDMA much greater than (+)-methamphetamine. Combination of two drugs at their EC50 did not cause more release than either drug alone at an equivalent concentration. In addition, the 5-HT uptake blockers fluoxetine and cocaine inhibited the release induced by MDMA, methamphetamine, PCA and fenfluramine to the same percentage. However, threshold concentrations of the substituted amphetamines known to inhibit uptake did not attenuate the release caused by higher concentrations of these compounds. These results suggests that MDMA, methamphetamine, PCA and fenfluramine cause 5-HT release via a common mechanism. Furthermore, these results indicate that the 5-HT uptake blockade induced by these substituted amphetamines in vitro is different from that induced by either fluoxetine or cocaine.