VARENICLINE BINDS WITH HIGH AFFINITY AND SELECTIVITY AT A 4 SS 2 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS. THE EFFICACY OF CHAMPIX IN SMOKING CESSATION IS BELIEVED TO BE THE RESULT OF VARENICLINEβS ACTIVITY AT A SUB-TYPE OF THE NICOTINIC RECEPTOR WHERE ITS BINDING PRODUCES AGONIST ACTIVITY, WHILE SIMULTANEOUSLY PREVENTING NICOTINE BINDING TO A 4 SS 2 RECEPTORS.
VARENICLINE BINDS TO A 4 SS 2 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS AND STIMULATES RECEPTOR-MEDIATED ACTIVITY, BUT AT A SIGNIFICANTLY LOWER LEVEL THAN NICOTINE. VARENICLINE BLOCKS THE ABILITY OF NICOTINE TO ACTIVATE A 4 SS 2 RECEPTORS AND THUS TO STIMULATE THE CENTRAL NERVOUS MESOLIMBIC DOPAMINE SYSTEM, BELIEVED TO BE THE NEURONAL MECHANISM UNDERLYING REINFORCEMENT AND REWARD EXPERIENCED UPON SMOKING. VARENICLINE IS HIGHLY SELECTIVE AND BINDS MORE POTENTLY TO A 4 SS 2 RECEPTORS THAN TO OTHER COMMON NICOTINIC RECEPTORS (>500-FOLD A 3 SS 4 , >3500- FOLD A 7 , >20,000-FOLD A 1 SS?D), OR TO NON-NICOTINIC RECEPTORS AND TRANSPORTERS (>2000-FOLD). VARENICLINE ALSO BINDS WITH MODERATE AFFINITY (KI = 350 NM) TO THE 5-HT3 RECEPTOR.