What occurs with alpha-methyl substitution of acetylcholine?

What occurs with alpha-methyl substitution of acetylcholine?

• A. Greater nicotinic than muscarinic selectivity
• B. Greater muscarinic than nicotinic selectivity
• C. No change in selectivity
• D. Loss of activity

Answer: (C)

Small changes near the ester linkage of acetylcholine mainly affect how quickly the molecule is broken down, not which receptor it prefers. Adding an alpha-methyl group makes the molecule more resistant to acetylcholinesterase, so it lasts longer in the synapse. This increased duration applies to both muscarinic and nicotinic receptors, because the alteration doesn’t preferentially improve binding to one receptor type over the other. So there’s no shift in selectivity between nicotinic and muscarinic receptors; the alpha-methyl substituted acetylcholine simply has a longer action without changing its receptor preference.

Small changes near the ester linkage of acetylcholine mainly affect how quickly the molecule is broken down, not which receptor it prefers. Adding an alpha-methyl group makes the molecule more resistant to acetylcholinesterase, so it lasts longer in the synapse. This increased duration applies to both muscarinic and nicotinic receptors, because the alteration doesn’t preferentially improve binding to one receptor type over the other. So there’s no shift in selectivity between nicotinic and muscarinic receptors; the alpha-methyl substituted acetylcholine simply has a longer action without changing its receptor preference.