Receptor Pharmacology of MDMA and Related Hallucinogensa

The brain 5HT2 receptor appears to be the site of action for hallucinogenic PIAs and LSD, marking a major step in understanding the molecular pharmacology of hallucinogenic drugs. Radioactive hallucinogenic drugs revealed detailed properties of 5HT2 receptors, including their interaction with GTP-binding proteins. Autoradiographic studies showed an extensive cortical distribution of 5HT2 receptors and suggested that PIAs may be 5HT1C agonists. Radiolabeling combined with drug discrimination studies indicated that MDMA is amphetamine-like, not LSD-like, while MDA is both LSD-like and amphetamine-like. However, MDMA may act as a 5HT2 agonist at high dosages.

Study at a glance

Abstract

The data presented herein appear to strongly implicate the brain 5HT2 receptor as the site-of-action of the hallucinogenic PIAs and LSD. If so, this discovery represents a major step in understanding the molecular pharmacology of hallucinogenic drugs. Using radioactive hallucinogenic drugs, detailed properties of brain 5HT2 receptors indicating the interaction of 5HT2 receptors with GTP-binding proteins have been revealed. Autoradiographic studies have revealed an extensive cortical distribution of brain 5HT2 receptors; these studies have also suggested that the PIAs may be 5HT1C agonists. Radiolabeling studies in conjunction with drug discrimination studies indicate that MDMA is apparently "amphetamine-like" and not "LSD-like" while MDA is apparently both "LSD-like" and "amphetamine-like." However, MDMA does appear to possess the potential to act as a 5HT2 agonist at high dosages.