In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys.
Experimental and Clinical Psychopharmacology February 1, 2008 DOI: 10.1037/1064-1297.16.1.1 via OpenAlex
Summary
AI-generated from the abstractThe chiral nature of the MDMA molecule produces two enantiomers, each biologically active. Reviewing the author's research and other publications, no differences between racemic MDMA and its enantiomers in maintaining behavior were noted. Blocking the 5-HT2A receptor shifted the dose-effect function rightward for S(+)-MDMA but insurmountably reduced the reinforcing effects of R(-)-MDMA. Long-term self-administration can lead to chronic tolerance, with S(+)-MDMA somewhat less susceptible than the racemate or R(-)-enantiomer. PET neuroimaging showed negligible dopamine transporter occupancy after R(-)-MDMA but reasonable interaction after S(+)-MDMA. Non-human primate studies caution that results with enantiomers may not inform about the racemate and vice versa.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Population | Non-human primates |
| Interventions | MDMA S(+)-MDMA R(-)-MDMA |
| Topics | MDMA Serotonin |
| Keywords | Enantiomer Pharmacology In vivo Dopamine |
| Citations | 30 |
| Key finding | The two enantiomers of MDMA differ in their interaction with the 5-HT2A receptor and dopamine transporter, and long-term tolerance to reinforcing effects varies between them. |
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.