Varenicline is prescribed to a 40-year-old man who smokes 20 cigarettes daily and wants to quit. Its therapeutic effect in reducing both craving and the rewarding effect of nicotine is explained by which pharmacological property?
- A Inhibition of dopamine and noradrenaline reuptake
- B Competitive antagonism at mu-opioid receptors
- C Partial agonist activity at alpha4-beta2 nicotinic acetylcholine receptors ✓
- D Irreversible blockade of monoamine oxidase
Correct answer: C. Partial agonist activity at alpha4-beta2 nicotinic acetylcholine receptors
Explanation
Varenicline is a partial agonist at the alpha4-beta2 subtype of the nicotinic acetylcholine receptor. Partial agonism provides modest mesolimbic dopamine release to reduce craving and withdrawal, while simultaneously occupying the receptor so smoked nicotine produces less reinforcement. Option A describes bupropion's mechanism. Opioid antagonism describes naltrexone, and MAO inhibition is not used for smoking cessation because of hypertensive risk with tyramine.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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