Which mechanism best explains the antihypertensive action and the characteristic adverse effect profile of reserpine?

• A Competitive antagonism of alpha-1 receptors on vascular smooth muscle
• B Stimulation of central alpha-2 receptors reducing sympathetic outflow
• C Irreversible inhibition of vesicular monoamine transporter, depleting norepinephrine stores centrally and peripherally ✓
• D Blockade of norepinephrine release from sympathetic nerve terminals by interfering with the calcium-dependent exocytosis

Explanation

Reserpine binds VMAT2 irreversibly, preventing storage of norepinephrine and other monoamines in vesicles; the transmitter leaks into cytoplasm and is degraded by mitochondrial MAO, depleting both central and peripheral stores. The resulting adrenergic deficit lowers blood pressure but also causes depression, which limits its use. Option A describes prazosin, option B describes methyldopa and clonidine, and option D describes guanadrel-type adrenergic neuron blockers.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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