NIMH Psychoactive Drug Screening Program, Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, United States of America.
PLoS One. 2013;8(3):e59334. doi: 10.1371/journal.pone.0059334. Epub 2013 Mar 19.
In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)-2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.
在本文中，我们通过国立精神卫生研究所精神药物筛选计划的资源，确定了目前用作“设计药物”的新型氯胺酮和苯环利定类似物的药理学特征，并将它们与母体物质进行了比较。氯胺酮类似物甲氧基氯胺酮（（RS）-2-（乙基氨基）-2-（3-甲氧基苯基）环己酮）和 3-MeO-PCE（N-乙基-1-（3-甲氧基苯基）环己胺）以及苯环利定的 3-和 4-甲氧基类似物，（1-[1-（3-甲氧基苯基）环己基]哌啶和 1-[1-（4-甲氧基苯基）环己基]哌啶），都是谷氨酸 NMDA 受体上 PCP 位点的高亲和力配体。此外，甲氧基氯胺酮和 PCP 及其类似物对 5-羟色胺转运体表现出相当大的亲和力，而 PCP 类似物对 sigma 受体表现出高亲和力。NMDA 受体的拮抗作用被认为是分离麻醉剂作用的关键药理学特征。新型氯胺酮和 PCP 类似物在放射性配体结合测定中对 NMDA 受体具有显著的亲和力，这可能解释了它们在人类使用者中的致幻作用。对其他靶点的额外作用对于描绘副作用可能很重要。
