Yongkang Fang, Yuanbing Lu, Suiqiang Zhu, Shanshan Huang
Hyperkinetic movement disorders, including dystonia and choreiform syndromes, are pathophysiologically linked to dysregulated dopamine metabolism within the basal ganglia-thalamo-cortical (BGTC) circuitry. Mounting research highlights dopaminergic hyperactivity as a driver of aberrant signaling and motor symptoms. Vesicular monoamine transporters (VMATs) package monoamines into synaptic vesicles, yet they remain pharmacologically underexplored compared to plasma membrane transporters. Recent advances in VMAT2 inhibitors offer a promising therapeutic avenue for hyperkinetic movement disorders. As a selectivity VMAT2 inhibitor, deutetrabenazine demonstrates unique advantages in dopamine modulation due to deuterium isotope-mediated metabolic stabilization, which extends the dynamics of dopamine receptor occupancy and reduces fluctuations in plasma concentration. Clinically, deutetrabenazine has emerged as a significant therapeutic approach for hyperkinetic movement disorders, with substantial evidence supporting its efficacy in the treatment of chorea associated with Huntington's disease (HD), tardive dyskinesia (TD), and Tourette syndrome. Future research should prioritize large-scale randomized trials incorporating rigorous subgroup analyses and extended safety monitoring to assess the distinct role of deutetrabenazine in other types of hyperkinetic movement disorders. This review unpacks the workings of VMAT2 inhibitors, paying particular attention to deutetrabenazine's distinct metabolic profile, and assesses their clinical promise across the range of choreiform disorders to hyperkinetic dystonic syndromes.