Varenicline - an Anti-smoking Drug

In 2006, Pfi2er brought varenicline Champix in the EU, Chantix in the USA) to the market as a drug for smoking cessation. This compound is derived structurally from cytisine. 

Structure-activity investigations of numerous natural products with high activity and as the profile of a partial agonist at the nicotinic a4P2-receptor provided a suitable pharmacophore model. This suggested a core structure with a basic nitrogen, which is protonated under physiological conditions, and in most cases an electron-deficient aromatic system, which is separated by two or three C-C bonds. 

The partial agonistic activity was determined via a functional electrophysi-ological assay in Xenopus oocytes at 10 pM of the test compound relative to 10 pM of nicotine, or upon co-administration of both. These competition experiments demonstrated that varenicline possesses only 68% of the efficacy of nicotine, while the efficacy of nicotine itself is reduced to 34 %. Extensive in vivo studies showed that oral administration of varenicline raises the release of dopamine in the Nucleus accumbens, but on the other hand, it attenuates the effect of nicotine. 

---