MDAI

MDAI (5,6-methylenedioxy-2-aminoindane) is a conformationally constrained entactogen in which the amphetamine side chain is locked into a rigid aminoindane ring. In vitro it behaves as a substrate-type releaser acting preferentially at the serotonin and norepinephrine transporters with comparatively weak activity at the dopamine transporter, a profile that predicts empathogenic rather than strongly stimulant or euphoric effects. It was originally developed as a candidate non-neurotoxic MDMA analogue, and early rodent work found that MDAI alone did not deplete brain serotonin, although co-administration with a dopamine releaser restored long-term serotonergic damage. This dependence of neurotoxicity on dopaminergic co-activity has made MDAI an informative tool for dissociating the serotonergic and dopaminergic contributions to substituted-amphetamine toxicity.