BINDING OF ALPHA-DIHYDROTETRABENAZINE TO THE VESICULAR MONOAMINE TRANSPORTER IS STEREOSPECIFIC

被引：92

作者：

KILBOURN, M

LEE, L

VANDERBORGHT, T

JEWETT, D

FREY, K

机构：

[1] Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1995年 / 278卷 / 03期

关键词：

MONOAMINE TRANSPORTER; MONOAMINE; VESICLE; TETRABENAZINE;

D O I：

10.1016/0014-2999(95)00162-E

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (K-i=0.97+/-0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (K-i=2.2+/-0.3 mu M). Each isomer was then synthesized in carbon-ii labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-alpha-dihydrotetrabenazine showed selective and specific accumulations in regions of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be blocked by coinjection of unlabeled tetrabenazine. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.

引用

页码：249 / 252

页数：4

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