Abuse Liability Profile of Three Substituted Tryptamines
Michael B. Gatch, Michael J. Forster, Aaron Janowsky, Amy J. Eshleman
Journal of Pharmacology and Experimental Therapeutics April 8, 2011 DOI: 10.1124/jpet.111.179705 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | DIPT 5-MeO-DET 5-MeO-AMT |
| Topics | LSD MDMA Psilocybin Serotonin |
| Keywords | Hallucinogen Methamphetamine Pharmacology Dopamine Monoamine neurotransmitter Abuse liability Reuptake Tryptamines Receptor |
| Citations | 42 |
| Key points | DIPT, 5-MeO-DET, and 5-MeO-AMT produced behavioral and receptor effects similar to abused hallucinogens but not psychostimulants, with DIPT and 5-MeO-DET showing full substitution for DMT and potential abuse liability. |
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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 25
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- Recreational Use, Analysis and Toxicity of Tryptamines Current Neuropharmacology December 10, 2014
- Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalling Swiss Medical Weekly January 11, 2015
and 20 more in the library
Cites 14
- Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics May 1, 2004
- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
- Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Addiction December 20, 2006
- Hallucinogens and dissociative agents naturally growing in the United States. Pharmacology & Therapeutics May 1, 2004
- Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. Journal of Neural Transmission September 12, 2009
and 9 more in the library