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Neurosci."],"published-print":{"date-parts":[[2011,5,11]]},"abstract":"<jats:p><jats:sc>l<\/jats:sc>-3,4-Dihydroxyphenylalanine (<jats:sc>l<\/jats:sc>-DOPA) is the most effective treatment for Parkinson's disease, but long-term<jats:sc>l<\/jats:sc>-DOPA administration is marred by the emergence of motor complications, namely, dyskinesia and a shortening of antiparkinsonian benefit (wearing-OFF). 3,4-Methylenedioxymethamphetamine (MDMA) is unique in that it exerts antidyskinetic effects and may enhance antiparkinsonian actions of<jats:sc>l<\/jats:sc>-DOPA. MDMA is composed of two enantiomers with different pharmacological profiles; here, we describe a novel enantiospecific synthesis of the two enantiomers and expand on the previous characterization of their pharmacology.<jats:italic>R<\/jats:italic>-MDMA (rectus-MDMA) is relatively selective for 5-HT<jats:sub>2A<\/jats:sub>receptors, whereas<jats:italic>S<\/jats:italic>-MDMA (sinister-MDMA) inhibits both serotonin (SERT) and dopamine transporters (DAT; SERT\/DAT ratio of 10 to 1).<jats:italic>R<\/jats:italic>- or<jats:italic>S<\/jats:italic>-MDMA (1, 3, and 10 mg\/kg, s.c.) was administered in combination with<jats:sc>l<\/jats:sc>-DOPA (15 mg\/kg, s.c.) to six female common marmosets (<jats:italic>Callithrix jacchus<\/jats:italic>) rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration. Motor disability, including parkinsonism and dyskinesia, and duration of antiparkinsonian benefit (ON-time) were evaluated. After the administration of<jats:italic>R<\/jats:italic>-MDMA (3 and 10 mg\/kg), the severity of peak-dose dyskinesia was decreased (by 33 and 46%, respectively;<jats:italic>p<\/jats:italic>&lt; 0.05); although total ON-time was unchanged (\u223c220 min), the duration of ON-time with disabling dyskinesia was decreased by 90 min when compared to<jats:sc>l<\/jats:sc>-DOPA alone (69% reduction;<jats:italic>p<\/jats:italic>&lt; 0.05).<jats:italic>S<\/jats:italic>-MDMA (1 mg\/kg) increased the total ON-time by 88 min compared to<jats:sc>l<\/jats:sc>-DOPA alone (34% increase;<jats:italic>p<\/jats:italic>&lt; 0.05), though dyskinesia were exacerbated. These data suggest that racemic MDMA exerts simultaneous effects, reducing dyskinesia and extending ON-time, by 5-HT<jats:sub>2A<\/jats:sub>antagonism and SERT-selective mixed monoamine uptake inhibition, which arise from its<jats:italic>R<\/jats:italic>and<jats:italic>S<\/jats:italic>enantiomers, respectively.<\/jats:p>","DOI":"10.1523\/jneurosci.1171-11.2011","type":"journal-article","created":{"date-parts":[[2011,5,11]],"date-time":"2011-05-11T20:23:40Z","timestamp":1305145420000},"page":"7190-7198","source":"Crossref","is-referenced-by-count":81,"title":["Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) Enantiomers<i>In Vitro<\/i>and in the MPTP-Lesioned Primate:<i>R<\/i>-MDMA Reduces Severity of Dyskinesia, Whereas<i>S<\/i>-MDMA Extends Duration of ON-Time"],"prefix":"10.1523","volume":"31","author":[{"given":"Philippe","family":"Huot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie D.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Koprich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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