21.03 Varenicline

A new drug that may be useful is varenicline (Champix). Varenicline is a partial agonist at a subtype of nicotinic receptors, nicotinic α4β2 receptors. As a partial agonist, varenicline exerts a lower maximum response that the endogenous ligand acetylcholine or nicotine (Figure 21.2). By mimicking the effect of nicotine, varenicline is able to promote the release of dopamine, and prevent the cravings observed with withdrawal from smoking cigarettes. Partial agonists with high affinity are capable of removing agonists with less affinity from a receptor. Varenicline has a higher for the nicotinic α4β2 receptors than nicotine, so will displace nicotine from the receptor. This is believed to block the effect of nicotine (from cigarettes) to cause re-inforcement.

Figure 21.2 Partial agonist varenicline (Copyright Sheila Doggrell, QUT)

Varenicline is more effective than nicotine replacement therapy, giving quit rates of about 20% at one year.

Unfortunately, when varenicline was made available to large numbers of people, it was shown to worsen neuropsychiatric illness in some, and it is now contraindicated in subjects with neuropsychiatric illness. Varenicline also comes with a warning to monitor subjects taking varenicline to make sure that a neuropsychiatric illness does not develop.