In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.
Experimental and Clinical Psychopharmacology – February 01, 2008
Source: OpenAlex
Summary
MDMA's two enantiomers exhibit distinct biological behaviors, with significant implications for pharmacology. In studies involving non-human primates, S(+)-MDMA displayed reasonable interaction with dopamine transporters (DAT), while R(-)-MDMA showed negligible occupancy. Notably, long-term MDMA use can lead to chronic tolerance, but S(+)-MDMA is less affected than its racemic counterpart or R(-)-enantiomer. Antagonism of the 5-HT2A receptor shifts the dose-response curve for S(+)-MDMA, while R(-)-MDMA's reinforcing effects are significantly diminished. Understanding these nuances is crucial for advancing forensic toxicology and drug analysis.
Abstract
The chiral nature of the MDMA molecule gives rise to two enantiomers, each of which is biologically active. This review attempts to cover the author's research into the in vivo effects of MDMA and its enantiomers, as well as other relevant publications which pertain to this topic. No particular differences between the capacities of racemic MDMA and its enantiomers to maintain behavior were noted, but antagonism of the 5-HT2A receptor produces a parallel rightward shift in the dose-effect function for the S(+)-enantiomer, but insurmountably reduces the reinforcing effects of R(-)-MDMA. Long-term self-administration of MDMA may lead to the development of chronic tolerance to the reinforcing effects of MDMA, but S(+)-MDMA is somewhat less susceptible to this effect than the racemate or the R(-)-enantiomer. Using PET neuroimaging, negligible occupancy at the dopamine transporter (DAT) was observed following administration of R(-)-MDMA, but reasonable DAT interaction was quantified following injection of S(+)-MDMA. The non-human primate studies reviewed herein caution that any results obtained in vivo with the MDMA enantiomers may not be particularly informative with regards to the racemate and vice versa.