title: Carane derivative stereoisomers of different local anaesthetic and antiplatelet activity similarly potentiate forskolin-stimulated cyclic AMP response and bind to beta-adrenoceptors in the rat brain cortex.
abstract: A carane derivative, KP-23 [RS](-)-4-(2-hydroxy-3)N-isopropylamino)-propoxyimino)-cis-carane, was earlier described as a potential local anaesthetic and antiplatelet agent, and the following studies revealed that its R and S stereoisomers, KP-23R and KP-23S, have different potencies in the infiltration anaesthesia and platelet aggregation tests. The effects of these stereoisomers on the cyclic AMP (cAMP) generating system and the displacement of [(3)H]CGP 12177 (a beta-adrenoceptor ligand) from its binding sites in the rat cerebral cortical tissue were investigated. The stereoisomers did not affect the basal cAMP level, but, at concentrations between 10(-4) and 10(-3) M, they elevated the forskolin-induced accumulation of cAMP with similar potency. The compounds displaced [(3)H]CGP 12177, however the stereoisomer R was less potent than the racemic KP-23 and the S form (K(i) = 64.1 +/- 5.9 nM, 161.1 +/- 10 nM and 62.1 +/- 5.6 nM for KP-23, KP-23R and KP-23S, respectively). The fact that the stereoisomers differed in both tests only slightly, if at all, suggests that their pharmacological effects are not related to the action on the beta-adrenoceptor/adenylate cyclase system.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland. mflibrow@cyf-kr.edu.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Vetulani
authors.forename: Irena
authors.initials: I
authors.lastname: Nalepa
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000081008:Bicyclic Monoterpenes; D002540:Cerebral Cortex / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003514:Cyclohexylamines / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology*; D013237:Stereoisomerism
chemical_list: D000779:Anesthetics, Local; D000081008:Bicyclic Monoterpenes; D003514:Cyclohexylamines; D011943:Receptors, Adrenergic, beta; C079300:4-(2-hydroxy-3-(N-isopropylamino)propoxyimino)carane; D005576:Colforsin; D000242:Cyclic AMP