Mescaline, a classical psychedelic, primarily acts on serotonin 5-HT2A/C receptors but also binds to 5-HT1A and 5-HT2B receptors. In adult male rats, the highest dose (100 mg/kg) caused hyperlocomotion, which was reversed by almost all antagonists tested. Sensorimotor gating deficits, measured as prepulse inhibition of acoustic startle, were selectively normalized by a 5-HT2A antagonist, while a 5-HT2C antagonist partially reversed deficits from lower doses. These findings indicate that mescaline's behavioral effects are mainly mediated by the 5-HT2A receptor subtype, with a lesser role for 5-HT2C receptors, and limited involvement of other subtypes.
Mescaline, a classical psychedelic with a phenylethylamine structure, primarily acts on serotonin 5-HT2A/C receptors but also binds to 5-HT1A and 5-HT2B receptors. Although it was the first psychedelic ever isolated and synthesized, the precise role of these different serotonin receptor subtypes in its behavioral pharmacology remains not fully understood.