PDF(Pubmed)
Abstract：
With a rising demand of cocaine over the last years, it is likely that unregulated new psychoactive substances with similar effects such as indatraline ((1R,3S)-3-(3,4-dichlorophenyl)-N-methyl-2,3-dihydro-1H-inden-1-amine) and troparil (Methyl (1R,2S,3S,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate) become popular as well. Both substances share a similar pharmacological profile as cocaine, while their potency is higher, and their duration of action is longer. This study investigated their metabolic fate in rat urine and incubations using pooled human liver S9 fraction (pHLS9). Indatraline formed two phase I and four phase II metabolites, with aromatic hydroxylation and glucuronidation being the main metabolic steps. All metabolites were detected in rat urine, while the parent compound was not detectable. Although low in abundance, indatraline metabolites were well identifiable due to their specific isotopic patterns caused by chlorine. Troparil formed four phase I and three phase II metabolites, with demethylation being the main metabolic step. Hydroxylation of the tropane ring, the phenyl ring, and combinations of these steps, as well as glucuronidation, were found. Phase I metabolites were detectable in rat urine and pHLS9, while phase II metabolites were only detectable in rat urine.
摘要：
随着过去几年可卡因需求的增加，可能是不受管制的具有类似作用的新精神活性物质，如indatraline((1R，3S）-3-（3,4-二氯苯基）-N-甲基-2,3-二氢-1H-inden-1-胺）和troparil（甲基（1R，2S,3S,5S）-8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯）也变得流行。这两种物质的药理作用与可卡因相似，虽然它们的效力更高，他们的行动持续时间更长。这项研究使用合并的人肝S9级分（pHLS9）研究了它们在大鼠尿液和孵育中的代谢命运。Indatraline形成两个I相和四个II相代谢物，芳香羟基化和葡糖醛酸化是主要的代谢步骤。在大鼠尿液中检测到所有代谢产物，而母体化合物检测不到。虽然丰度低，indatraline代谢物由于其由氯引起的特定同位素模式而被很好地识别。Troparil形成了四个I相和三个II相代谢物，去甲基化是主要的代谢步骤。三氯环的羟基化，苯环,以及这些步骤的组合，以及葡糖醛酸化，被发现了。在大鼠尿液和pHLS9中可检测到I相代谢物，而II相代谢物仅在大鼠尿液中可检测到。
