Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes

The enantiomers of MDA, PMA, and MDMA, along with their alpha,alpha-dimethylated derivatives, were tested for their ability to release serotonin from rat whole brain synaptosomes. At bath concentrations of 1 and 10 micrometers, the amphetamine isomers potently induced serotonin release, but were inactive at 0.1 micrometers. At 1 micrometer, the (+) isomer of MDMA was more effective than the (-) isomer, and because the (+) isomer is the clinically active form, this suggests that transmitter release may contribute to MDMA's biological activity. The alpha,alpha-dimethyl compounds did not release serotonin even at the highest concentration.

Study at a glance

Abstract

The enantiomers of 3,4-(methylenedioxy)amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their alpha, alpha-dimethylated derivatives, were evaluated for an effect on the release of [3H]serotonin from rat whole brain synaptosomes. The amphetamine isomers were all potent in inducing the release of [3H]serotonin at bath concentrations of 1 and 10 micrometers but were inactive at 0.1 micrometers. No significant difference in isomer potency was observed at the 10 micrometers concentration. However, at 1 micrometer the (+) isomer of MDMA was more effective in inducing release than was the (-) isomer. Since it is the (+) isomer which is clinically active, this result suggests that transmitter release may play a role in the biological activity of MDMA. By contrast, the alpha, alpha-dimethyl compounds were not effective in releasing serotonin, even at the highest bath concentration.