The therapeutic potential of cytisine and its derivatives in disorders of the central nervous system.

Cytisine is a quinolizidine alkaloid that is widely used in smoking cessation, exerting its neurological and other biological actions primarily through binding to the nicotinic acetylcholine receptor (nAChR). Cytisine binds to the nAChR (herein represented by α4β2) and exhibits distinct receptor recognition characteristics that provide a basis for the structural optimization of its derivatives in terms of affinity and selectivity. An increasing number of studies indicate that cytisine and its derivatives exhibit a variety of neuroprotective and functional benefits in disorders of the central nervous system (CNS), including Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, depression, and ischemic stroke. In this review, the binding interactions between cytisine and nAChR are discussed extensively. Then the neuroprotective roles of cytisine and its derivatives in CNS diseases are summarized, and cellular and molecular mechanisms are further highlighted. This review aims to provide a basis for further research and to promote the possible clinical application of cytisine and its derivatives. Taken together, cytisine and its derivatives may provide promising drug candidates to treat a range of CNS diseases.