Replacing one methyl group on the nitrogen of acetylcholine with an ethyl or propyl group would result in:

Replacing one methyl group on the nitrogen of acetylcholine with an ethyl or propyl group would result in:

• A. Still an active cholinergic agonist but less potent than acetylcholine
• B. Inactive
• C. A selective nicotinic antagonist
• D. Increased potency

Answer: (C)

Increasing the size of one substituent on the quaternary nitrogen of acetylcholine changes how that molecule interacts with receptor binding sites. The compound remains positively charged and can still resemble acetylcholine enough to fit into receptor pockets, but the bulkier ethyl or propyl group introduces steric hindrance that prevents the precise orientation and conformational change needed to activate the receptor. At nicotinic receptors, this bulky analog can bind but fail to trigger channel opening, effectively blocking acetylcholine—acting as an antagonist. The muscarinic receptor binding and activation rely on a different interaction geometry, and the increased bulk often reduces efficacy there, so the analog doesn’t act as an agonist at muscarinic sites. Thus, this modification would produce a selective nicotinic antagonist.

Increasing the size of one substituent on the quaternary nitrogen of acetylcholine changes how that molecule interacts with receptor binding sites. The compound remains positively charged and can still resemble acetylcholine enough to fit into receptor pockets, but the bulkier ethyl or propyl group introduces steric hindrance that prevents the precise orientation and conformational change needed to activate the receptor.

At nicotinic receptors, this bulky analog can bind but fail to trigger channel opening, effectively blocking acetylcholine—acting as an antagonist. The muscarinic receptor binding and activation rely on a different interaction geometry, and the increased bulk often reduces efficacy there, so the analog doesn’t act as an agonist at muscarinic sites. Thus, this modification would produce a selective nicotinic antagonist.