Where does fentanyl bind, and what locks it in place?

• A. Binds to NMDA receptors and is locked by hydrogen bonds
• B. Binds to GABA receptors and is locked by covalent bonds
• C. Binds in the μ-opioid receptors' pockets and is locked by salt bridges
• D. Binds to nicotinic receptors and is locked by ionic interactions

Answer: (C)

Fentanyl achieves its potency by binding in the pockets of μ-opioid receptors, which are G-protein coupled receptors in the brain. The molecule has a tertiary amine that is positively charged at physiological pH, and this charge forms a salt bridge with an acidic residue in the receptor’s binding site (for example, an aspartate). That ionic interaction acts as the lock, anchoring fentanyl securely in the pocket. In addition, hydrophobic and aromatic contacts within the pocket help stabilize the complex, contributing to high affinity and strong analgesic effects. The other receptor types listed are not the primary targets for fentanyl, and covalent bonding is not how this drug binds; the key idea is noncovalent salt-bridge locking within the μ-opioid receptor pocket.