Discriminative Stimulus Effects of 3,4- Methylenedioxymethamphetamine and Its Enantiomers in Mice: Pharmacokinetic Considerations

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse with mixed stimulant- and hallucinogen-like effects. The aims of the present studies were to establish discrimination of S()-MDMA, R()-MDMA, or their combination as racemic MDMA in separate groups of mice to assess cross-substitution tests among all three compounds, to determine the time courses of the training doses, to assess pharmacokinetic vari-ables after single injections and after cumulative dosing, and to define the metabolic dispositions of MDMA enantiomers and their metabolites. All three forms of MDMA served as discrim-inative stimuli, and with the exception of R()-MDMA in mice trained to discriminate the racemate, compounds substituted for one another. The onset of interoceptive effects for S()-MDMA and racemic MDMA were faster than for R()-MDMA