methamphetamine, p-chloroamphetamine and fenfiuramine induce 5-hydroxytryptamine release via a common mechanism blocked by fluoxetine and cocaine

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 microassaysystem. The rank order of release potencies was found to be (+)PCA = ( +)-fenfluramine > (+)-MDMA >>( +)methamphetamine.Combination of two drugs at their ECs0 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, metharaphetamine,PCA and fenfiuramine to the same percentage. However, threshold concentrations of the substituted amphetaminesknown to inhibit uptake did not attenuate the release caused by higher concentrations of these compounds. These resultssuggests that MDMA, methamphetamine, PCA and fenfiuramine cause 5-HT release via a common mechanism. Farthermore, these results indicate-that the 5-HT uptake blockade induced by these substituted amphetamines in vitro is different fromthatinducedbyeitherfluoxetine orcocaine. ' a