Rickli Anna, Moning Olivier D, Hoener Marius C, Liechti Matthias E
Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Neuroscience Research, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Eur Neuropsychopharmacol. 2016 Aug;26(8):1327-37. doi: 10.1016/j.euroneuro.2016.05.001. Epub 2016 May 20.
The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties.
本研究调查了新型精神活性色胺类物质二异丙基色胺（DiPT）、4-羟基二异丙基色胺（4-OH-DiPT）、4-羟基-N,N-二甲基色胺（4-OH-MET）、5-甲氧基-N,N-二甲基色胺（5-MeO-AMT）和5-甲氧基-N-甲基-N-异丙基色胺（5-MeO-MiPT）与单胺受体和转运体之间的相互作用，并与经典致幻剂麦角酸二乙酰胺（LSD）、脱磷酸裸盖菇素、N,N-二甲基色胺（DMT）和三甲氧苯乙胺进行了比较。我们研究了它们与人单胺受体的结合亲和力，并测定了功能性5-羟色胺（5-羟色胺[5-HT]）5-HT2A和5-HT2B受体的激活情况。还测定了它们与人单胺摄取转运体的结合及对其的抑制作用，以及转运体介导的单胺释放情况。所有新型色胺均与5-HT2A受体相互作用，且为部分或完全5-HT2A激动剂。与LSD相比，所有色胺（包括脱磷酸裸盖菇素和DMT）对5-HT2A受体的结合亲和力均较低，且与人类报告的精神活性剂量相关。包括脱磷酸裸盖菇素、DMT、DiPT、4-羟基二异丙基色胺和4-羟基-N,N-二甲基色胺在内的几种色胺与5-羟色胺转运体相互作用，对去甲肾上腺素转运体也有部分作用，类似于3,4-亚甲基二氧甲基苯丙胺，但与LSD和三甲氧苯乙胺不同。LSD而非色胺与肾上腺素能和多巴胺能受体相互作用。总之，色胺的受体相互作用谱预示其致幻作用与经典的5-羟色胺能致幻剂相似，但也具有类似摇头丸的精神活性特性。
