Dihydrotetrabenazine is an active metabolite of the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine that is generated by hepatic carbonyl reductases. Dihydrotetrabenazine binds to mouse pons medulla, hypothalamus, and striatum (Kds = 2.72, 2.28, and 2.4 nM, respectively) and inhibits synaptic vesicular serotonin (5-HT) uptake (IC50s = 2.2, 2.8, and 2.3 nM, respectively). It also binds to human caudate nucleus, hippocampus, and substantia nigra pars compacta (Kds = 2.9, 2.5, and 2.8 nM, respectively). Dihydrotetrabenazine stereoisomers bind to VMAT2 in rat striatum.