(-)-Cytisine and Derivatives: Synthesis, Reactivity, and Applications

Cytisine has a high affinity at nicotinic acetylcholine receptors (nAChRs)10-14 with high α4β2 subtype selectivity. It behaves as a partial agonist with low nonspecific binding. Cytisine has appeared as a lead candidate to develop new molecules interacting more selectively with the nAChRs of the central nervous system (CNS) while displaying minimal side effects. Cytisine was first isolated in 1865 by Husemann and Marmeé from the seeds of Cytisus Laburnum Med., a small hardy tree common in central and southern Europe and cultivated for its golden-yellow flowers. The binding characteristics of [3H]cytisine to brain membrane preparations have been extensively studied since 1980. Freedman, Sloan, and Anderson research groups demonstrated that the dissociation constant (KD) of [3H]cytisine for rat brain nAChRs was less than 1 nM10 (0.145 nM). The Ferger group in 1998 demonstrated that cytisine can induce a reduction of hydroxyl radical production in vitro.