In experimental preparations, hemicholinium and vesamicol both reduce acetylcholine output from cholinergic neurons. They differ because:

• A Hemicholinium blocks choline uptake into the terminal while vesamicol blocks transport of acetylcholine into storage vesicles ✓
• B Hemicholinium blocks vesicular transport while vesamicol blocks high-affinity choline uptake
• C Hemicholinium inhibits choline acetyltransferase while vesamicol degrades acetylcholine
• D Both drugs inhibit choline acetyltransferase but differ in their site of binding

Explanation

Acetylcholine synthesis begins with high-affinity uptake of extracellular choline into the nerve terminal, the rate-limiting step, which hemicholinium blocks. Vesamicol acts one step later, preventing transport of newly synthesized acetylcholine from cytosol into the storage vesicle via the vesicular acetylcholine transporter. Neither drug inhibits choline acetyltransferase itself. Knowing which step each drug interrupts is the discriminating fact examiners test with this pair.

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

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