title: Synthesis and preliminary pharmacological evaluation of some cytisine derivatives.
abstract: Thirty-one N-derivatives of cytisine were prepared in order to modify its pharmacological profile and to obtain compounds of potential therapeutic interest either at a peripheral or central level, particularly as nicotinic ligands with improved ability to cross the blood-brain barrier. Actually, with 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) and 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 Ki values in the range 30-163 nM.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Canu Boido
authors.forename: F
authors.initials: F
authors.lastname: Sparatore
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001392:Azocines; D001667:Binding, Competitive; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D011807:Quinolizines; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic / Q000187:drug effects; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D013055:Spectrophotometry, Infrared; D000093843:Quinolizidine Alkaloids
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D001392:Azocines; D018678:Cholinergic Agents; D007004:Hypoglycemic Agents; D008024:Ligands; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011807:Quinolizines; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D011978:Receptors, Nicotinic; D018005:Receptors, Vasoactive Intestinal Peptide; C004712:cytisine; D000093843:Quinolizidine Alkaloids