Abuse Liability Profile of Three Substituted Tryptamines
Journal of Pharmacology and Experimental Therapeutics – April 08, 2011
Source: OpenAlex
Summary
DIPT and 5-MeO-DET may pose significant abuse risks similar to known hallucinogens. In a study with rats, DIPT fully substituted for DMT and DOM at doses of 1.71 mg/kg and 1.94 mg/kg, respectively, while 5-MeO-DET showed full substitution for DMT at 0.41 mg/kg. Notably, DIPT achieved only 68% LSD-appropriate responding. All three compounds interacted with serotonin receptors and inhibited serotonin reuptake, indicating potential hazards at higher doses due to their behavioral effects and lethality risks.
Abstract
The abuse liability profile of three synthetic hallucinogens, N,N-diisopropyltryptamine (DIPT), 5-N,N-diethyl-5-methoxytryptamine (5-MeO-DET), and 5-methoxy-α-methyltryptamine (5-MeO-AMT), was tested in rats trained to discriminate hallucinogenic and psychostimulant compounds, including cocaine, methamphetamine, 3,4-methylenedioxymethylamphetamine (MDMA), lysergic acid diethylamide (LSD), (-)-2,5-dimethoxy-4-methylamphetamine (DOM), and dimethyltryptamine (DMT). Because abused hallucinogens act at 5-hydroxytryptamine 1A (5-HT(1A)) and 5-HT(2A) receptors, and abused psychostimulants act at monoamine transporters, binding and functional activities of DIPT, 5-MeO-DET, and 5-MeO-AMT at these sites were also tested. DIPT fully substituted in rats trained to discriminate DMT (ED(50) = 1.71 mg/kg) and DOM (ED(50) = 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED(50) = 0.41 mg/kg) and produced 59% MDMA-appropriate responding. 5-MeO-AMT did not fully substitute for any of the training drugs, but produced 67% LSD-appropriate responding. None of the compounds produced substitution in rats trained to discriminate cocaine or methamphetamine. All three compounds showed activity at 5-HT(1A) and 5-HT(2A) receptors as well as blockade of reuptake by the serotonin transporter. In addition, 5-MeO-AMT produced low levels of serotonin release and low potency blockade of dopamine uptake. DIPT, 5-MeO-DET, and 5-MeO-AMT produced behavioral and receptor effects similar to those of abused hallucinogens, but were not similar to those of psychostimulants. DIPT and 5-MeO-DET may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality.