Differences in Dihydrotetrabenazine Isomer Concentrations Following Administration of Tetrabenazine and Valbenazine

ConclusionsBased on relative abundance and potency, [+]- β-HTBZ appears to be the primary contributor to VMAT2 inhibition by TBZ, a finding in contrast with the generally held assertion that [+]-α-HTBZ is the major contributor. [−]-α-HTBZ, the other abundant TBZ metabolite, has much lower VMAT2 inhibitory potency than [+]-β-HTBZ, but increased affin ity for other CNS targets, which may contribute to off-target effects of TBZ. In contrast, pharmacological activity for VBZ is derived primarily from [+]-α-HTBZ. Individual HTBZ isomer concentrations provide a more clinically relevant endpoint for assessing on- and off-target effects of TBZ than to tal isomer concentrations.
Source: Drugs in R&D - Category: Drugs & Pharmacology Source Type: research