Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, USA.
J Pharmacol Exp Ther. 2011 Jul;338(1):280-9. doi: 10.1124/jpet.111.179705. Epub 2011 Apr 7.
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.
三种合成致幻剂，N,N-二异丙基色胺（DIPT）、5-N,N-二乙基-5-甲氧基色胺（5-MeO-DET）和 5-甲氧基-α-甲基色胺（5-MeO-AMT）的滥用倾向特征在经过训练以区分致幻剂和苯丙胺类兴奋剂（包括可卡因、甲基苯丙胺、3,4-亚甲基二氧甲基苯丙胺（MDMA）、麦角酸二乙酰胺（LSD）、（-）-2,5-二甲氧基-4-甲基苯丙胺（DOM）和二甲色胺（DMT））的大鼠中进行了测试。因为被滥用的致幻剂作用于 5-羟色胺 1A（5-HT(1A)）和 5-HT(2A)受体，而被滥用的苯丙胺类兴奋剂作用于单胺转运体，所以还测试了 DIPT、5-MeO-DET 和 5-MeO-AMT 在这些部位的结合和功能活性。DIPT 完全取代了训练用于区分 DMT（ED(50) = 1.71 mg/kg）和 DOM（ED(50) = 1.94 mg/kg）的大鼠，但是只产生了 68%的 LSD 适当反应。5-MeO-DET 完全取代了 DMT（ED(50) = 0.41 mg/kg），并产生了 59%的 MDMA 适当反应。5-MeO-AMT 未能完全取代任何一种训练药物，但产生了 67%的 LSD 适当反应。没有一种化合物在训练用于区分可卡因或甲基苯丙胺的大鼠中产生取代。所有三种化合物在 5-HT(1A)和 5-HT(2A)受体以及对 5-羟色胺转运体的再摄取阻断方面均有活性。此外，5-MeO-AMT 产生了低水平的 5-羟色胺释放和低效力的多巴胺摄取阻断。DIPT、5-MeO-DET 和 5-MeO-AMT 产生了与被滥用的致幻剂相似的行为和受体效应，但与苯丙胺类兴奋剂不相似。DIPT 和 5-MeO-DET 的滥用倾向可能与已知的致幻剂相似，并且可能具有危害性，因为高剂量会产生活性和致死性。
