Psychopharmacology
July 2, 2014
Theresa M. Carbonaro, Amy J. Eshleman, Michael J. Forster et al.
67 citations
The 5-HT2A receptor plays a major role in mediating the effects of the hallucinogens DMT and DiPT. A 5-HT2A receptor inverse agonist fully blocked the discriminative stimulus effects of DMT but only partially blocked those of DiPT. A 5-HT2C receptor antagonist partially attenuated DiPT's effects but minimally affected DMT. An mGluR2/3 agonist produced potent but partial blockade of DMT's effects, while an mGluR2/3 antagonist facilitated the effects of both compounds. Both DMT and DiPT induced head twitches, with DiPT producing more, and these were blocked by a 5-HT2A receptor inverse agonist. DiPT acted as a low-potency full agonist at the 5-HT2C receptor in vitro. The findings suggest that 5-HT2C and mGluR2 receptors modulate the effects of these tryptamine hallucinogens to some degree.
Journal of Pharmacology and Experimental Therapeutics
April 8, 2011
Michael B. Gatch, Michael J. Forster, Aaron Janowsky et al.
42 citations
Three synthetic hallucinogens—DIPT, 5-MeO-DET, and 5-MeO-AMT—produced behavioral effects in rats similar to those of known abused hallucinogens like LSD and DMT, but not to psychostimulants like cocaine or methamphetamine. DIPT fully substituted for DMT and DOM, while 5-MeO-DET fully substituted for DMT; none fully substituted for cocaine or methamphetamine. All three compounds acted at serotonin 5-HT(1A) and 5-HT(2A) receptors and blocked serotonin reuptake. 5-MeO-AMT also weakly released serotonin and blocked dopamine uptake. DIPT and 5-MeO-DET may have abuse liability similar to hallucinogens and were hazardous at high doses, causing activity and lethality.
J Pharmacol Exp Ther
January 20, 2023
Laura B. Kozell, Amy J. Eshleman, Tracy L. Swanson et al.
40 citations
Substituted tryptamines show varying potency and selectivity at serotonin receptors and the serotonin transporter. Several compounds, including 5-MeO-DMT and 5-MeO-tryptamine, are potent 5-HT2AR agonists, while others like 5-MeO-NMT and bufotenine have lower activity. At 5-HT2CR, 5-MeO-DMT and 5-MeO-tryptamine are also potent, but bufotenine is inactive. Most tryptamines have weak or no activity at 5-HT1AR and the serotonin transporter. The findings indicate that the 5-methoxy substitution enhances 5-HT2AR and 5-HT2CR potency, while the N,N-dimethyl group is important for high efficacy.