Ketamine is a common anesthetic used in human and veterinary medicine. This drug has recently received increased medical and scientific attention due to its indications for neurological diseases. Despite being applied for decades, ketamine’s entire metabolism and pharmacological profile have not been elucidated yet. Therefore, insights into the metabolism and brain distribution are important toward identification of neurological effects. Herein, we have investigated ketamine and its metabolites in the pig brain, cerebrospinal fluid, and plasma using mass spectrometric and metabolomics analysis. We discovered previously unknown metabolites and validated their chemical structures. Our comprehensive analysis of the brain distribution of ketamine and 30 metabolites describes significant regional differences detected mainly for phase II metabolites. Elevated levels of these metabolites were identified in brain regions linked to clearance through the cerebrospinal fluid. This study provides the foundation for multidisciplinary studies of ketamine metabolism and the elucidation of neurological effects by ketamine.

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新氯胺酮代谢物的鉴定及其在哺乳动物大脑中的详细分布

氯胺酮是人类和兽医中常用的麻醉剂。由于其治疗神经系统疾病的适应症，这种药物最近受到越来越多的医学和科学关注。尽管已应用数十年，但氯胺酮的整个代谢和药理学特征尚未阐明。因此，了解新陈代谢和大脑分布对于识别神经系统影响非常重要。在此，我们利用质谱和代谢组学分析研究了猪脑、脑脊液和血浆中的氯胺酮及其代谢物。我们发现了以前未知的代谢物并验证了它们的化学结构。我们对氯胺酮和 30 种代谢物的大脑分布的综合分析描述了主要针对 II 期代谢物检测到的显着区域差异。在与脑脊液清除相关的大脑区域中发现了这些代谢物水平升高。这项研究为氯胺酮代谢的多学科研究和阐明氯胺酮对神经系统的影响奠定了基础。