The drug MDMA, composed of two mirror-image forms (enantiomers), shows promise for treating Parkinson's disease motor complications. R-MDMA reduced peak-dose dyskinesia severity by 33% at 3 mg/kg and 46% at 10 mg/kg, and cut the duration of disabling dyskinesia by 69% (90 minutes) without changing total ON-time. S-MDMA at 1 mg/kg extended total ON-time by 34% (88 minutes) but worsened dyskinesia. The findings suggest that racemic MDMA's simultaneous antidyskinetic and ON-time-extending effects arise from R-MDMA's action on 5-HT2A receptors and S-MDMA's inhibition of serotonin and dopamine transporters.
Homochiral (R)- and (S)-MDMA were synthesized in six steps from d- and l-alanine. A copper-catalyzed regioselective ring-opening of an N-tosylaziridine with an aryl Grignard reagent gave high yields and complete regioselectivity. The synthesis preserved configurational integrity, yielding R- and S-MDMA hydrochlorides with enantiopurities greater than 99.5%, confirmed by enantioselective HPLC with fluorescence detection. Applying the same method to make homochiral enantiomers of the α-phenyl analogue UWA-001 failed due to a switch in regioselectivity in the key step.