Varenicline for tobacco dependence

Abstract

A 57-year-old man with a 60-pack-year history visits his primary care provider because he wants to quit smoking. He has a history of stable coronary artery disease, peripheral vascular disease, and hypertension. He also has severe obstructive lung disease (forced expiratory volume in 1 second, 39% of the predicted value) with a progressive increase in dyspnea. He has quit smoking and has had numerous relapses; the longest duration of abstinence from smoking was 7 months. Each relapse involved casual smoking to “test himself.” During previous attempts to quit, he has used a nicotine patch, a nicotine inhaler, and sustained-release bupropion. He feels motivated to quit smoking because he recently heard about a new medication to aid in quitting, and he wants to improve his health. The patient and his physician discuss the therapeutic options and agree that varenicline (Chantix) may be an option.

Figure 1. The Actions of Nicotine and Varenicline in the Brain

The principal site of nicotine action in the brain is the mesolimbic system (Panel A). Nicotine stimulates dopaminergic neurons located in the ventral tegmental area, increasing dopamine release in the nucleus accumbens. Nicotine interacts with nicotinic acetylcholine receptors, which are pentameric ion channels located in the mesolimbic system and elsewhere (Panel B). The highest-affinity nicotinic acetylcholine receptors consist of two α4 subunits and three β2 subunits. Nicotine binds to and causes a conformational change in the α4β2 nicotinic acetylcholine receptor, increasing sodium (Na⁺) influx. Varenicline is a partial agonist of the α4β2 nicotinic acetylcholine receptor that causes partial stimulation while it competitively inhibits nicotine binding.