Which approach is used to optimize cholinergic agonists by increasing receptor selectivity?

• A. Increasing lipophilicity
• B. Increasing selectivity to muscarinic and nicotinic receptors
• C. Increasing stability to gastric acid and esterases
• D. Decreasing molecular weight

Answer: (B)

The key idea is tuning a cholinergic agonist to bind preferentially to a specific acetylcholine receptor subtype, increasing its receptor selectivity for muscarinic or nicotinic receptors. By adjusting molecular features that interact with the receptor binding pocket, chemists can bias affinity toward one type of receptor, improving therapeutic effects and reducing unwanted activation of the other subtype. This is why the best choice is increasing selectivity to muscarinic and nicotinic receptors—it directly targets receptor subtype engagement. The other options affect pharmacokinetic properties like absorption, stability, or molecular size, rather than how the drug binds to its receptor.