Characterization of brain interactions with methylenedioxyamphetamine and methylenedioxymethamphetamine.

Brain recognition sites have been identified for [3H]MDA and [3H]MDMA. The dissociation constants of MDA and MDMA for these sites are similar to the concentrations needed to affect several brain neurochemical parameters and are in keeping with concentrations of MDA in brain (165 microM) following administration of behaviorally active doses (20 mg/kg) of the drug. While the characteristics of these binding sites suggest a possible hydrophobic interaction with brain membranes, this interaction is not without specificity, since it has a unique pharmacology and a heterogeneous distribution in brain. Similarities have been found between [3H]MDA binding studied in the present report and that of apparent 3Hamphetamine binding studied by Hauger et al. (1984). Both have extremely high Bmax values, are optimal in p2 preparations, are stabilized by sucrose, and share similar patterns of regional distribution. Measuring the specific binding of [3H]amphetamine, [3H]fenfluramine, [3H]MDA, and related compounds under identical conditions will be required to determine the possible relationships among the interactions of these compounds with brain membranes. Further study is also needed to determine the possible importance such interactions of amphetamine and its substituted analogs may have with brain membranes in relation to the pharmacology of these substances.