Varenicline is indicated for cessation of smoking.
Nicotine acts in the brain by binding to the nicotinergic acetylcholine receptors of the subtype α4β2. The activated receptor induces dopamine release in the mesolimbic pathway which results in a reward effect and in dependence when used chronically (A). This strong reward signal mediated by dopamine keeps up the addiction via the nucleus accumbens. See also the graphic below for the distribution of these receptors in the different brain areas: cortex, hippocampus and mainly in the ventral tegmentum from which the mesolimbic and mesocortical routes project. When a smoker quits acutely, the α4β2-receptor will not be activated anymore and the reward signal does not occur. Due to the acute stop of the dopaminergic activation a craving signal now occurs
instead (B). Varenicline is a partial agonist of the nicotinergic acetylcholine α4β2-receptor (C). When it is used with smoking cessation, it will partially activated the receptor resulting in less craving signals, but also a decreased reward signal (nicotine cannot bind anymore).
So, varenicline can be used for quitting smoking because of two mechanisms: it acts as a partial agonist and thus reduces the symptoms of craving when quitting smoking, and it has antagonistic actions by binding the receptor instead of nicotine and therefore decreases the reward effect of nicotine.
The most important side effects of varenicline are nausea, vomiting, and headache.
After one year, 22% of the treated group continued to abstain from smoking.
EPAR of varenicline.