Guanethidine is an adrenergic neuron blocker that was formerly used for hypertension. It enters noradrenergic nerve terminals via which mechanism?

• A Active uptake by Uptake-1 (noradrenaline transporter, NET) ✓
• B Passive diffusion through the neuronal cell membrane
• C Active uptake by Uptake-2 (extraneuronal transporter, OCT)
• D Receptor-mediated endocytosis via alpha-2 autoreceptors

Explanation

Guanethidine enters sympathetic nerve terminals via the noradrenaline transporter (Uptake-1, NET) — the same transporter that normally recaptures released noradrenaline. Once inside, it displaces noradrenaline from vesicles and ultimately depletes noradrenaline stores, blocking sympathetic transmission. Tricyclic antidepressants, cocaine, and amphetamines, which block Uptake-1, prevent guanethidine entry and abolish its antihypertensive effect. This is a clinically important pharmacokinetic drug interaction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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