Receptor selectivity of cytisinicline: minimal 5-HT3 binding may explain lower incidence of nausea in smoking cessation therapy

This study provides pharmacologic evidence that cytisinicline selectively interacts with the α4β2 nicotinic receptor while exhibiting minimal interaction with the 5-HT3 receptor, a key mechanism potentially underlying its improved gastrointestinal tolerability. These findings help explain the lower nausea rates observed in clinical trials and support cytisinicline as a promising alternative to varenicline for smoking cessation, particularly in individuals sensitive to medication-related side effects. This receptor-specific profile may enhance treatment adherence and expand the appeal of pharmacologic smoking cessation strategies.