Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors
Pharmacology Biochemistry and Behavior November 1, 1998 Roger Smith 142 citations
DMT acts as an agonist at both 5-HT2A and 5-HT2C receptors, activating the main intracellular signaling pathway (phosphoinositide hydrolysis) to a degree comparable to serotonin. In rats trained to discriminate between a 5-HT2A antagonist and agonist, DMT fully substituted for the agonist DOI, confirming its agonist activity at 5-HT2A receptors. At 5-HT2C receptors in native choroid plexus, DMT was a partial agonist. A key difference: the 5-HT2C receptor desensitized profoundly to DMT over time, while the 5-HT2A receptor did not. This may explain why DMT's hallucinogenic effects do not show tolerance in humans, suggesting the 5-HT2C receptor plays a lesser role in DMT's action.