Smoking is the main preventable cause worldwide of morbidity and premature death. At current rates of smoking, about half of all smokers in the USA and the UK will die prematurely of tobacco‐related diseases (DOH 1998; Fiore 2004). The list of illnesses known to be linked to smoking is rapidly expanding, and now includes cancers of the cervix, pancreas, kidneys and stomach, aortic aneurisms, acute myeloid leukemia, cataracts, pneumonia and gum disease. These are in addition to the long‐established links between tobacco use and such illnesses as lung cancer, cardiovascular diseases, and emphysema, and with prematurity, sudden infant death syndrome and low birth weight in the babies of maternal smokers (Surgeon General 2004).

Innovative drugs for smoking cessation are increasingly building upon a growing understanding of the neurochemistry of nicotine addiction (Fagerstrom 2006). There is compelling evidence that dependence upon nicotine reflects the effects of the drug at neuronal nicotinic receptors in the brain (Benowitz 1999; Picciotto 1999). More recent studies have explored the potential of neuronal nicotinic acetylcholine receptors (nAChRs) as targets for a variety of therapeutic interventions (Hogg 2004). It is thought that the addictive properties of nicotine are mediated through its action as an agonist at α4β2 nAChRs, which stimulates the release of dopamine (Coe 2005).

The Pfizer research team which set out to develop a drug to counteract the effects of nicotine on the nAChRs started with the naturally‐occurring alkaloid compound cytisine, which had been shown to be an effective partial agonist for α4β2 receptors (Papke 1994; Slater 2003). Cytisine was developed as a treatment for tobacco dependence in the Soviet Union in the 1960s, and is still commercially available in Bulgaria and through internet sales, under the trade name of Tabex (Foulds 2004). Its manufacurers, Sopharma Pharmaceuticals, developed their phytoproduct from the plant Cytisus Laborinum L. (Golden Rain).

Varenicline was developed in 1997 (Coe 2005), and is described as a selective nicotinic receptor partial agonist. It was designed to selectively activate the α4β2nAChR, mimicking the action of nicotine and causing a moderate and sustained release of mesolimbic dopamine (Sands 2005). This, it was suggested, should counteract withdrawal symptoms consequent upon low dopamine release during smoking cessation attempts. However, because it is a partial agonist at these receptors, it does not elicit the substantial increases in dopamine overflow evoked by nicotine and, perhaps more importantly, it blocks the effects of a subsequent nicotine challenge on dopamine release from the mesolimbic neurones thought pivotal to the development of nicotine dependence (Coe 2005).

Trials of cytisine have been conducted in Bulgaria, Germany and Poland, and trials of varenicline are currently underway or in the preliminary report stage in the USA.