5F-MDMB-PICA代谢物鉴定和大麻素受体活性。,Drug Testing and Analysis

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5F-MDMB-PICA代谢物鉴定和大麻素受体活性。
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2019-09-10 , DOI: 10.1002/dta.2688
Michael T Truver ₁ , Shimpei Watanabe ₂ , Anna Åstrand ₃ , Svante Vikingsson _{2,

3} , Henrik Green _{2,

3} , Madeleine J Swortwood ₁ , Robert Kronstrand _{2,

3}

Affiliation

根据欧洲药物和药物成瘾监测中心（EMCDDA）的数据，截至2017年，报告了179种不同的合成大麻素。在美国，5F‐MDMB‐PINACA或5F‐ADB占大麻素缉获量的28％2016– 2018。合成大麻素5F‐MDMB‐PICA在结构上类似于5F‐MDMB‐PINACA，但吲哚基取代了吲唑。这些合成大麻素的体内或体外代谢研究数据有限，因此可能会漏掉鉴定其用途的潜在代谢产物。这项研究的目的是（a）利用人肝细胞研究5F‐MDMB‐PICA和5F‐MDMB‐PINACA的体外代谢；（b）通过分析真实病例标本来验证体外代谢产物；（c）通过检查认证机构的活动来确定5F‐MDMB‐PICA和5F‐MDMB‐PINACA的效力和功效_1个受体。在这项研究中发现的生物转化包括I期转化和II期转化。总共鉴定出22种5F‐MDMB‐PICA代谢产物（A1至A22）。从肝细胞温育和尿液样本中，鉴定出21种代谢物（B1至B21）以及5F‐MDMB‐PINACA尿液样本独特的3种化合物。在5F-MDMB-PICA（n = 3）和5F-MDMB-PINACA（n = 5）。对于这两种化合物，酯水解和酯水解结合氧化脱氟是体外产生的最普遍的代谢产物。此外，首次将5F‐MDMB‐PICA的酯水解氧化脱氟转化为戊酸。因此，这些代谢物可能是筛选疑似5F-MDMB-PICA或5F-MDMB-PINACA中毒尿液的潜在生物标记。5F‐MDMB‐PICA和5F‐MDMB‐PINACA均是CB ₁受体的完全激动剂，具有更高的功效，且效力与JWH‐018相似。

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5F-MDMB-PICA metabolite identification and cannabinoid receptor activity.

According to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), there were 179 different synthetic cannabinoids reported as of 2017. In the USA, 5F‐MDMB‐PINACA, or 5F‐ADB, accounted for 28% of cannabinoid seizures 2016–2018. The synthetic cannabinoid, 5F‐MDMB‐PICA, is structurally similar to 5F‐MDMB‐PINACA with an indole group replacing the indazole. Limited data exist from in vivo or in vitro metabolic studies of these synthetic cannabinoids, so potential metabolites to identify use may be missed. The goals of this study were to (a) investigate 5F‐MDMB‐PICA and 5F‐MDMB‐PINACA in vitro metabolism utilizing human hepatocytes; (b) to verify in vitro metabolites by analyzing authentic case specimens; and (c) to identify the potency and efficacy of 5F‐MDMB‐PICA and 5F‐MDMB‐PINACA by examining activity at the CB₁ receptor. Biotransformations found in this study included phase I transformations and phase II transformations. A total of 22 5F‐MDMB‐PICA metabolites (A1 to A22) were identified. From hepatocyte incubations and urine samples, 21 metabolites (B1 to B21) were identified with 3 compounds unique to urine specimens for 5F‐MDMB‐PINACA. Phase II glucuronides were identified in 5F‐MDMB‐PICA (n = 3) and 5F‐MDMB‐PINACA (n = 5). For both compounds, ester hydrolysis and ester hydrolysis in combination with oxidative defluorination were the most prevalent metabolites produced in vitro. Additionally, the conversion of ester hydrolysis with oxidative defluorination to pentanoic acid for the first time was identified for 5F‐MDMB‐PICA. Therefore, these metabolites would be potentially good biomarkers for screening urine of suspected intoxication of 5F‐MDMB‐PICA or 5F‐MDMB‐PINACA. Both 5F‐MDMB‐PICA and 5F‐MDMB‐PINACA were acting as full agonists at the CB₁ receptor with higher efficacy and similar potency as JWH‐018.

更新日期：2019-09-10

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