Zheng Guangrong, Dwoskin Linda P, Crooks Peter A
College of Pharmacy, University of Kentucky, Department of Pharmaceutical Sciences, Lexington, KY 40536-0082, USA.
AAPS J. 2006 Nov 10;8(4):E682-92. doi: 10.1208/aapsj080478.
In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is the only transporter that moves cytoplasmic dopamine (DA) into synaptic vesicles for storage and subsequent exocytotic release. Pharmacologically enhancing DA sequestration by VMAT2, and thus preventing the oxidation of DA in the cytoplasm, may be a strategy for treating diseases such as Parkinson's disease. VMAT2 may also be a novel target for the development of treatments for psychostimulant abuse. This review summarizes the possible role of VMAT2 as a therapeutic target, VMAT2 ligands reported in the literature, and the structure-activity relationship of these ligands, including tetrabenazine analogs, ketanserin analogs, lobeline analogs, and 3-amine-2-phenylpropene analogs. The molecular structure of VMAT2 and its relevance to ligand binding are briefly discussed.
在中枢神经系统中，囊泡单胺转运体2（VMAT2）是唯一将细胞质多巴胺（DA）转运至突触小泡进行储存并随后通过胞吐作用释放的转运体。通过VMAT2在药理学上增强DA的隔离，从而防止细胞质中DA的氧化，可能是治疗帕金森病等疾病的一种策略。VMAT2也可能是开发治疗精神兴奋剂滥用药物的新靶点。本综述总结了VMAT2作为治疗靶点的可能作用、文献中报道的VMAT2配体以及这些配体的构效关系，包括丁苯那嗪类似物、酮色林类似物、洛贝林类似物和3-胺-2-苯基丙烯类似物。简要讨论了VMAT2的分子结构及其与配体结合的相关性。
