Comprehensive metabolic investigation of dopamine reuptake inhibitor HDMP-28 in equine liver microsomes and Cunninghamella elegans for doping control,Drug Testing and Analysis

当前位置： X-MOL 学术 › Drug Test. Anal. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Comprehensive metabolic investigation of dopamine reuptake inhibitor HDMP-28 in equine liver microsomes and Cunninghamella elegans for doping control
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2024-01-15 , DOI: 10.1002/dta.3642
Meleparappil Muhammed Ajeebsanu ₁ , Michael Benedict Subhahar ₁ , Abdul Khader Karakka Kal ₁ , Moses Philip ₁ , Zubair Perwad ₁ , Tajudheen Kunhamu Karatt ₁ , Fatma Mohammed Graiban ₁ , Marina Joseph ₂ , Shantymol V Jose ₂

Affiliation

A dopamine reuptake inhibitor is a type of medication or substance that works by blocking the reuptake of dopamine in the brain. Dopamine reuptake inhibitors offer multiple effects, including increased alertness, improved mood, and therapeutic potential for conditions like depression, ADHD, and Parkinson's disease. HDMP-28, or methylnaphthidate, is a potent synthetic stimulant from the phenyltropane class. It surpasses methylphenidate in both dopamine reuptake inhibition and half-life. As a dopamine reuptake inhibitor, it boosts dopamine levels by hindering reuptake into nerve cells, resulting in heightened stimulation and increased energy. In order to comprehensively address both the tangible and potential repercussions of the unauthorized utilization of the aforementioned substance in sports, it is imperative to establish analytical methodologies for the identification of the parent drug and its primary metabolites. Additionally, a comprehensive analysis of the metabolic characteristics of HDMP-28 in both human and animal subjects has yet to be published. This study explores the metabolic conversion of HDMP-28 mediated by equine liver microsomes and Cunninghamella elegans. An extraction and detection method was developed, optimized, and validated for doping assessment in equine urine and plasma. Liquid chromatography–high-resolution mass spectrometry was employed to determine metabolite structures. The study identified 31 (22 phase I and 9 phase II) metabolites of HDMP-28, including hydroxylated, hydrogenated, and hydrolyzed analogs. Glucuronic acid-conjugated metabolites were also detected. This manuscript describes metabolites based on the in vitro studies, which might not be the same in vivo. These findings aid in the detection and understanding of the illicit use of HDMP-28 in equestrian sports.

中文翻译：

多巴胺再摄取抑制剂 HDMP-28 在马肝微粒体和秀丽隐杆线虫中的综合代谢研究，用于兴奋剂控制

多巴胺再摄取抑制剂是一种通过阻止大脑中多巴胺的再摄取起作用的药物或物质。多巴胺再摄取抑制剂具有多种功效，包括提高警觉性、改善情绪以及治疗抑郁症、多动症和帕金森病等疾病的潜力。 HDMP-28（或萘甲酸甲酯）是苯托烷类的有效合成兴奋剂。它在多巴胺再摄取抑制和半衰期方面均超过哌醋甲酯。作为多巴胺再摄取抑制剂，它通过阻碍神经细胞的再摄取来提高多巴胺水平，从而增强刺激和增加能量。为了全面解决体育运动中未经授权使用上述物质的实际和潜在影响，必须建立鉴定母体药物及其主要代谢物的分析方法。此外，HDMP-28 在人类和动物受试者中代谢特征的综合分析尚未发表。本研究探讨了马肝微粒体和秀丽隐杆线虫介导的 HDMP-28 代谢转化。开发、优化和验证了一种提取和检测方法，用于马尿液和血浆中的兴奋剂评估。采用液相色谱-高分辨率质谱测定代谢物结构。该研究鉴定了 HDMP-28 的 31 种代谢物（22 种 I 期和 9 种 II 期），包括羟基化、氢化和水解类似物。还检测到葡萄糖醛酸结合的代谢物。本手稿描述的代谢物是基于体外研究，在体内可能不一样。这些发现有助于检测和了解 HDMP-28 在马术运动中的非法使用。

更新日期：2024-01-17

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11