A 60-year-old man with schizophrenia treated for many years with haloperidol develops orofacial choreoathetotic movements. Tetrabenazine is chosen for treatment. Its therapeutic effect is mediated by:

• A Competitive blockade of striatal D2 receptors
• B Reversible inhibition of vesicular monoamine transporter 2, depleting stored striatal dopamine ✓
• C Irreversible inhibition of monoamine oxidase B in the basal ganglia
• D Partial agonism at presynaptic D2 autoreceptors

Explanation

Tardive dyskinesia reflects dopaminergic supersensitivity in the striatum after chronic D2 blockade. Tetrabenazine reversibly inhibits VMAT2, the transporter that packages monoamines into synaptic vesicles, thereby depleting releasable dopamine and reducing the involuntary movements. It does not block postsynaptic D2 receptors, so it carries little risk of causing parkinsonism itself, though depression is a recognised adverse effect. Reserpine acts similarly but irreversibly and on peripheral stores, making it unsuitable here.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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