TY - JOUR
T1 - Abuse liability profile of three substituted tryptamines
AU - Gatch, Michael B.
AU - Forster, Michael J.
AU - Janowsky, Aaron
AU - Eshleman, Amy J.
PY - 2011/7
Y1 - 2011/7
N2 - 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-HT1A) and 5-HT2A 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 (ED50 = 1.71 mg/kg) and DOM (ED50 = 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED50 = 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-HT1A and 5-HT2A 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.
AB - 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-HT1A) and 5-HT2A 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 (ED50 = 1.71 mg/kg) and DOM (ED50 = 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED50 = 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-HT1A and 5-HT2A 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.
UR - http://www.scopus.com/inward/record.url?scp=79959528477&partnerID=8YFLogxK
U2 - 10.1124/jpet.111.179705
DO - 10.1124/jpet.111.179705
M3 - Article
C2 - 21474568
AN - SCOPUS:79959528477
SN - 0022-3565
VL - 338
SP - 280
EP - 289
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -