5-MeO-DIPT, a hallucinogenic drug similar to DMT, produced head-twitch responses in mice, an effect blocked by a serotonin 2A receptor antagonist. In rats trained to recognize LSD, 5-MeO-DIPT partially substituted for LSD (75% generalization) and suppressed response rates in a dose-dependent way; this effect was abolished by a 5-HT2A antagonist but not by a 5-HT1A antagonist. The drug showed micromolar affinity for 5-HT2A and 5-HT2C receptors and much higher affinity for 5-HT1A receptors in rat brain tissue. The results indicate that the 5-HT2A receptor is a key site of action for 5-MeO-DIPT, despite its in vitro selectivity for the 5-HT1A receptor.
MDMA (ecstasy) has two mirror-image forms, or enantiomers, that produce different effects: one acts more like a stimulant, the other more like a hallucinogen. In mice trained to recognize one or the other enantiomer, a stimulant drug fully substituted only for the stimulant-like enantiomer, and a hallucinogen-like drug fully substituted only for the hallucinogen-like enantiomer. Cocaine and a tryptamine hallucinogen substituted for both, but each was more potent for one enantiomer than the other. These results indicate that the two enantiomers of MDMA produce qualitatively distinct internal sensations in mice, helping explain the drug's complex psychoactive profile.