Carane derivative stereoisomers of different local anaesthetic and antiplatelet activity similarly potentiate forskolin-stimulated cyclic AMP response and bind to β-adrenoceptors in the rat brain cortex

Abstract

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 [3H]CGP 12177 (a β-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 10−3m, they elevated the forskolin-induced accumulation of cAMP with similar potency. The compounds displaced [3H]CGP 12177, however the stereoisomer R was less potent than the racemic KP-23 and the S form (Ki = 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 β-adrenoceptor/adenylate cyclase system.