Neostigmine reverses non-depolarizing neuromuscular blockade by inhibiting acetylcholinesterase. Which additional mechanism contributes to its neuromuscular reversal that is NOT shared by pyridostigmine?

• A Direct agonist action at nicotinic receptors at the NMJ
• B Enhanced presynaptic acetylcholine release via prejunctional nicotinic receptor stimulation ✓
• C Inhibition of plasma cholinesterase
• D Blockade of potassium channels at the end-plate

Explanation

Neostigmine, in addition to acetylcholinesterase inhibition, has a direct facilitation of acetylcholine release from motor nerve terminals via stimulation of prejunctional nicotinic receptors — this amplifies the cholinergic effect at the NMJ and enhances reversal of block. Pyridostigmine relies primarily on AChE inhibition with no significant prejunctional action. Options A and D are not mechanisms of neostigmine, and option C describes an effect irrelevant to NMJ reversal.

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

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