Kilbourn, M
Lee, L
Vander Borght, Thierry
[UCL]
Jewett, D
Frey, K
The two enantiomers of alpha-dihydrotetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (Ki = 0.97 +/- 0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (Ki = 2.2 +/- 0.3 microM). Each isomer was then synthesized in carbon-11 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.
Bibliographic reference |
Kilbourn, M ; Lee, L ; Vander Borght, Thierry ; Jewett, D ; Frey, K. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific.. In: European journal of pharmacology, Vol. 278, no.3, p. 249-52 (1995) |
Permanent URL |
http://hdl.handle.net/2078.1/123332 |