期刊
ACTA PHARMACEUTICA SINICA B
卷 12, 期 8, 页码 3341-3353出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2022.03.018
关键词
Pharmacometabolomics; Pharmacokinetics; Pharmacodynamics; Mass spectrometry imaging; Antipsychotic drug
资金
- National Natural Science Foundation of China [81773678, 81974500]
- CAMS Innovation Fund for Medical Sciences (CIFMS) (China) [2021-I2M-1-026]
A temporal-spatial pharmacometabolomics method based on ambient mass spectrometry imaging was proposed and applied to evaluate the microregional effect of olanzapine on brain tissue. It accurately characterizes the pharmacokinetics and pharmacodynamics of olanzapine at the microregional level.
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. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据