In methacholine, which statement about enantiomers is true?

In methacholine, which statement about enantiomers is true?

• A. The R-enantiomer is more active than the S-enantiomer.
• B. The enantiomers have equal activity.
• C. The S-enantiomer is less active than the R-enantiomer.
• D. The S-enantiomer is more active than the R-enantiomer.

Answer: (D)

Chirality matters for how a drug fits its receptor. Methacholine has two mirror-image forms, and the muscarinic receptor that it activates is chiral, so the two enantiomers don’t bind equally. The S-enantiomer fits the receptor’s binding pocket in a way that allows key interactions to form efficiently, giving higher affinity and stronger agonist activity. The R-enantiomer adopts a less favorable orientation, reducing binding and efficacy. So the S-enantiomer is more active than the R-enantiomer.

Chirality matters for how a drug fits its receptor. Methacholine has two mirror-image forms, and the muscarinic receptor that it activates is chiral, so the two enantiomers don’t bind equally. The S-enantiomer fits the receptor’s binding pocket in a way that allows key interactions to form efficiently, giving higher affinity and stronger agonist activity. The R-enantiomer adopts a less favorable orientation, reducing binding and efficacy. So the S-enantiomer is more active than the R-enantiomer.