Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific

Article abstract of DOI:10.1016/0014-2999(95)00162-E

The two enantiomers of α-dihydratetrabenazine 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 μM). Each isomer was then synthesized in carbon-11 labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-α-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 α-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.