Differential inhibition of alpha 2-adrenoceptor-mediated pressor responses by (+)- and (-)-verapamil in pithed rats.
The inhibitory effects of (+)- and (-)-verapamil on the hypertensive responses brought about by the alpha 2-adrenoceptor agonist B-HT 920 were investigated in pithed normotensive rats. (-)-Verapamil was found to be about 4 times more potent with respect to depressing alpha 2-pressor responses compared with (+)-verapamil. To rule out the effect of 'unspecific' vasodilatation after the administration of the stereoisomers of verapamil, vasopressin was continuously infused into the carotid artery of pithed rats in a separate series of experiments. In the course of this vasopressin infusion, new inhibitory activities of the stereoisomers of verapamil on alpha 2-adrenoceptor-mediated pressor responses were determined. Under these circumstances, the potency ratio of (-)- vs (+)-verapamil was about 7. With the aid of a radioligand binding assay using [3H]clonidine to identify alpha 2-adrenoceptors, low affinities were measured for the stereoisomers of verapamil. A Ki = 6170 nM for (-)-verapamil and a Ki = 41700 nM for (+)-verapamil were calculated. The results indicate that the interaction between alpha 2-adrenoceptor-mediated pressor responses and calcium entry blockers, such as verapamil, is a stereoselective event.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology; D013237:Stereoisomerism; D014700:Verapamil / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001381:Azepines; C024763:talipexole; D014700:Verapamil; D003000:Clonidine