Liu Dan, Huang Jianpeng, Gao Shanshan, Jin Hongtao, He Jiuming
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Department of Clinical Pharmacy, First People's Hospital of Huaihua, Huaihua 418000, China.
Acta Pharm Sin B. 2022 Aug;12(8):3341-3353. doi: 10.1016/j.apsb.2022.03.018. Epub 2022 Mar 31.
The brain is the most advanced organ with various complex structural and functional microregions. It is often challenging to understand what and where the molecular events would occur for a given drug treatment in the brain. Herein, a temporo-spatial pharmacometabolomics method was proposed based on ambient mass spectrometry imaging and was applied to evaluate the microregional effect of olanzapine (OLZ) on brain tissue and demonstrate its effectiveness in characterizing the microregional pharmacokinetics and pharmacodynamics of OLZ for improved understanding of the molecular mechanism of drugs acting on the microregions of the brain. It accurately and simultaneously illustrated the levels dynamics and microregional distribution of various substances, including exogenous drugs and its metabolites, as well as endogenous functional metabolites from complicated brain tissue. The targeted imaging analysis of the prototype drug and its metabolites presented the absorption, distribution, metabolism, and excretion characteristics of the drug itself. Moreover, the endogenous functional metabolites were identified along with the associated therapeutic and adverse effects of the drug, which can reflect the pharmacodynamics effect on the microregional brain. Therefore, this method is significant in elucidating and understanding the molecular mechanism of central nervous system drugs at the temporo and spatial metabolic level of system biology.
大脑是最先进的器官，具有各种复杂的结构和功能微区。对于大脑中给定的药物治疗，了解分子事件会在何处以及发生了什么往往具有挑战性。在此，基于常压质谱成像提出了一种时空药物代谢组学方法，并将其应用于评估奥氮平（OLZ）对脑组织的微区效应，并证明其在表征OLZ的微区药代动力学和药效学方面的有效性，以更好地理解药物作用于脑微区的分子机制。它准确且同时地展示了各种物质的水平动态和微区分布，包括外源性药物及其代谢物，以及来自复杂脑组织的内源性功能代谢物。对原型药物及其代谢物的靶向成像分析呈现了药物本身的吸收、分布、代谢和排泄特征。此外，还鉴定了内源性功能代谢物以及药物相关的治疗和不良反应，这可以反映对脑微区的药效学作用。因此，该方法在系统生物学的时空代谢水平上阐明和理解中枢神经系统药物的分子机制方面具有重要意义。
