Cytisine, a natural plant alkaloid, has been marketed in Central and Eastern 
Europe for over 40 years for the clinical management of smoking cessation. 
Despite the fact that cytisine has been used by millions of smokers, its 
characteristics have not been reviewed in scientific literature in English, and 
presently existing clinical studies on its effectiveness and safety are 
insufficient to warrant licensing by modern standards. Understanding of the 
mechanism of cytisine action as a smoking cessation aid provides a necessary 
basis for conducting clinical trials to confirm its efficacy as an optimal 
antismoking therapy. Hereafter, we present a review of current knowledge about 
the pharmacokinetics, pharmacodynamics, toxicity, therapeutic efficacy and 
safety of cytisine, and about its derivatives that are under development. Recent 
pharmacological research has elucidated that the drug is a low efficacy partial 
agonist of alpha4beta2 nicotinic acetylcholine receptors, which are believed to 
be central to the effect of nicotine (NIC) on the reward pathway. The drug 
reduces the effects of NIC on dopamine release in the mesolimbic system when 
given alone, while simultaneously attenuating NIC withdrawal symptoms that 
accompany cessation attempts. Clinical studies on cytisine as a smoking 
cessation aid have demonstrated that the drug is effective and safe. Our recent 
uncontrolled trial has shown that a 12-month carbon monoxide-verified continuous 
abstinence rate following a standard course of treatment with cytisine with 
minimal behavioral support is similar (13.8%; N = 436) to that observed 
following treatment with NIC replacement therapy. Since cytisine exhibits a 
desirable pharmacological profile which makes it an attractive smoking cessation 
drug, it should be advanced to randomized clinical trials. However, more 
detailed preclinical studies on its pharmacokinetics and safety profile are 
required.