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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.
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