Synthesis and preliminary pharmacological evaluation of some cytisine derivatives

Thirty-one N-derivatives of cytisine were prepared in order to modify its p harmacological profile and to obtain compounds of potential therapeutic int erest either at a peripheral or central level, particularly as nicotinic li gands with improved ability to cross the blood-brain barrier. Actually, wit h the introduction of different kinds of substituent on the basic nitrogen of cytisine a variety of activities were observed, both in vivo (analgesic, dopamine antagonism, antihypertensive, inhibition of stress-induced ulcers , antiinflammatory, protection from PAF-induced mortality, hypoglycemic) an d in vitro (positive cardio-inotropic, beta-adrenergic antagonism, alpha(1) - and alpha(2)-antagonism, inhibition of PAF-induced platelet aggregation). Six randomly selected compounds were tested for the ability to recognize a central nicotinic receptor and four of them exhibited K-i values; In the r ange 30-163 nM. (C) 1999 Elsevier Science S.A. All rights reserved.