Valbenazine and deutetrabenazine, approved for tardive dyskinesia, improve abnormal movements through which mechanism?

• A Competitive blockade of striatal dopamine D2 receptors
• B Irreversible inhibition of monoamine oxidase B in the basal ganglia
• C Reversible inhibition of vesicular monoamine transporter 2, depleting presynaptic dopamine stores ✓
• D Stimulation of dopamine autoreceptors via selective D3 agonism

Explanation

Both drugs are reversible VMAT2 inhibitors that block packaging of dopamine into synaptic vesicles, reducing the amount released per impulse from nigrostriatal terminals, thereby dampening involuntary movements. This differs from tetrabenazine's older use and from antipsychotic therapy: option A would treat psychosis but can worsen parkinsonian features, and MAO-C inhibition would raise synaptic dopamine, aggravating dyskinesia.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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