title: Abuse liability profile of three substituted tryptamines.
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.
authors.affiliation: Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, USA. michael.gatch@unthsc.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gatch
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forster
authors.forename: Aaron
authors.initials: A
authors.lastname: Janowsky
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eshleman
mesh_terms: D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006213:Hallucinogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000378:metabolism*; D014363:Tryptamines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D006213:Hallucinogens; D014363:Tryptamines; D044282:Receptor, Serotonin, 5-HT1A; C026864:5-methoxy-alpha-methyltryptamine; C033695:N,N-diisopropyltryptamine; D012701:Serotonin