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Potential Pharmacokinetic Drug-Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist 期刊论文

编号：

7bd7f61b-3c19-4c06-b2d2-c83e22f335d1
作者：

Zhang, Yunpeng#^[1,2]Li, Shuping(李淑萍)^[1,2]Wang, Youxu^[1,2]Deng, Gang^[1,2]Cao, Ning^[1,2]Wu, Chao^[1,2]Ding, Wenzheng^[1,2]Wang, Yuwen^[1,2]Cheng, Xuemei(程雪梅)^[1,2,3]Wang, Changhong(王长虹)*^[1,2,3]
语种：

英文
期刊：

MOLECULES ISSN：1420-3049 2019 年 24 卷 7 期 ; APR 11
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关键词：

harmine memantine drug-drug interaction pharmacokinetics Alzheimer's disease liquid chromatography-mass spectrometry
摘要：

Harmine (HAR) is a beta-carboline alkaloid widely distributed in nature. It exhibits psychopharmacological effects of improving learning and memory. However, excessive dose of HAR can cause central tremor toxicity, which may be related to the glutamate system. Memantine (MEM) is a non-competitive N-methyl-d-aspartate receptor antagonist. It can be used for the treatment of Alzheimer's disease and also can block the neurotoxicity caused by glutamate. Therefore, combination of HAR and MEM would be meaningful and the pharmacokinetics investigation of HAR and MEM in combination is necessary. A ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the simultaneous quantitative determination of MEM, HAR and harmol (HOL), a main metabolite of HAR, in rat plasma after oral administration of HAR and MEM in combination (5.0 mg/kg of MEM combined with 20.0, 40.0, 80.0 mg/kg of HAR). The contents of HAR and HOL were determined after oral administration of HAR (20.0, 40.0 and 80.0 mg/kg), and the content of MEM was determined after oral administration of MEM (5.0 mg/kg). Blood samples were collected from each rat at 0 (pre-dose), 0.08, 0.17, 0.25, 0.33, 0.50, 0.75, 1.0, 2.0, 4.0, 8.0, 12.0 and 24.0 h after administration. The maximum peak concentration (C-max) of MEM was obviously decreased, and the area under the plasma concentration versus time curve from zero to time t (AUC((0-t))) and mean residence time (MRT) were significantly increased after combination with HAR. The C-max and AUC((0-t)) of HAR and its metabolite HOL were increased after combination with MEM. These findings suggested that co-administration of HAR and MEM could extend their residence time in rats, and then might increase the efficacy for treatment of Alzheimer's disease. Therefore, this study will provide a basis for the rational combined application of HAR and MEM.
推荐引用方式
GB/T 7714：

Zhang Yunpeng,Li Shuping,Wang Youxu, et al. Potential Pharmacokinetic Drug-Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist [J].MOLECULES,2019,24(7).
APA：

Zhang Yunpeng,Li Shuping,Wang Youxu,Deng Gang,&Wang Changhong.(2019).Potential Pharmacokinetic Drug-Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist .MOLECULES,24(7).
MLA：

Zhang Yunpeng, et al. "Potential Pharmacokinetic Drug-Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist" .MOLECULES 24,7(2019).
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