Discriminative stimulus effects of N,N-diisopropyltryptamine

Abstract

Rationale Serotonergic hallucinogens such as (+)-lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT) produce distinctive visual effects, whereas the synthetic hallucinogen N,N-diisopropyltryptamine (DiPT) is known for its production of auditory distortions. Objective: This study compares the discriminative stimulus effects of DiPT to those of visual hallucinogens. Methods Adult male rats were trained to discriminate DiPT (5 mg/kg, 15 min) from saline under a FR10 schedule. A dose-effect and time course of DiPT’s discriminative stimulus effects were established. DMT, (−)-2,5-dimethoxy-4-methylamphetamine (DOM), LSD, (±)-methylenedioxymethamphetamine (MDMA) and (+)-methamphetamine were tested for cross-substitution in DiPT-trained animals. Results Rats learned to discriminate DiPT from saline in an average of 60 training sessions (30 drug and 30 saline). DiPT (0.5 – 5 mg/kg) produced dose-dependent increases in drug-appropriate responding (DAR) to 99% (ED50 = 2.47 mg/kg). Onset of the discriminative stimulus effects was within 5 minutes and the effects dissipated within 4 hours. Full substitution for the discriminative stimulus effects of DiPT occurred with LSD, DOM and MDMA. DMT only partially substituted for DiPT (65% DAR), whereas (+)-methamphetamine failed to substitute for DiPT (29% DAR). Conclusions The discriminative stimulus effects of DiPT were similar those of a number of synthetic hallucinogens, only partially similar to those of DMT, but not similar to (+)-methamphetamine. The putative DiPT-induced auditory distortions do not lead to discriminative stimulus effects distinguishable from other hallucinogens.

The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice

“…It is also possible that the difference in the ability of MDL100907 to block the discriminative stimulus effects of DMT and DiPT is because the doses of the two compounds are not pharmacologically equivalent. Arguments against this possibility include: 1) the doses of DMT and DiPT used for training were the peak doses in cross-substitution studies with other hallucinogens (Gatch et al, 2009; 2011; Carbonaro et al, 2013) and produced similar amounts of rate suppression, and 2) MDL100907 attenuated DMT- and DiPT–induced head twitches proportionally. Finally, it is also possible that the difference is due to mice being used for head twitch and rats for drug discrimination.…”

“…Conversely, DiPT fully substituted in DOM-trained rats, produced around 70% DAR in LSD-trained rats and failed to substitute in MDMA-trained rats (Gatch et al, 2011). In DiPT-trained rats, LSD, DOM and MDMA produced full substitution (Carbonaro et al 2013). However, DMT and DiPT did not fully cross-substitute for each other.…”

Neuropharmacology of N,N-dimethyltryptamine

“…In contrast, other tryptamine hallucinogens produced more equivocal effects, with DiPT and 5-methoxy-diethyl tryptamine (5-MeO-DET) producing full substitution, 4-Hydroxy-N,N-diisopropyl tryptamine (4-OH-DiPT) and 5-methoxy-N-isopropyl-N-methyl tryptamine (5-MeO-IMPT) producing partial substitution, and 5-methoxy-α-methyl tryptamine (5-MeO-αMT) producing little if any DMT-like effects (Gatch et al 2009; 2011). In addition, although DiPT fully substituted in DMT-trained rats (Gatch et al, 2011), DMT only produced 65 % DAR in DiPT-trained rats (Carbonaro et al, 2013). Taken together, these findings indicate that serotonergic hallucinogens largely produce discriminative stimulus effects similar, but not entirely identical to those of DMT.…”

Recreational Use, Analysis and Toxicity of Tryptamines

“…Diisopropyl-tryptamine (DiPT) is a synthetic hallucinogen, structurally related to dimethyl-tryptamine, but, unlike DMT, which produces short term visual hallucinations, DiPT causes auditory distortions [ 36 ]. DiPT presents a similar molecular mechanism of action as other hallucinogens.…”