NBI-98782 (RRR-dihydrotetrabenazine, RRR-DHTBZ, (+)-α-HTBZ) is a potent, highly selective VMAT2 inhibitor (Ki=2 nM) and tetrabenazine metabolite.
RRR-DHTBZ displays >1000-fold selective in a broad-panel selectivity screen, including monoamine receptors.
RRR-DHTBZ displayed dose-dependent efficacy in both antipsychotic models (PPI and CAR) equivalent in magnitude to either typical or atypical antipsychotics.
RRR-DHTBZ elicited escape failures (indicative of sedation, ≥0.6 mg/kg) and at the highest dose tested produced catalepsy (motor inhibition, 1.2 mg/kg).
RRR-DHTBZ synergizes with the antipsychotics risperidone or olanzapine in suppressing conditioned avoidance behavior.
RRR-DHTBZ is effective in animal models of schizophrenia and potentiates the behavioral potency of antipsychotics in these models without potentiating weight gain.
