Analysis of the interaction between lacidipine and BAY K 8644 in two isolated rabbit arteries.
The calcium antagonist activity of the long-acting 1,4-dihydropyridine (DHP) lacidipine has been analyzed in rabbit ear artery (REA) and rabbit basilar artery (RBA). Its potency has been estimated from its interaction with BAY K 8644 using a three state gating model of the voltage-operated calcium channel. As a contractile agent, BAY K 8644 exhibited a bell-shaped concentration-response curve in both arteries. For fitting purposes, a second binding interaction between BAY K 8644 and the channel has been used to describe the descending part of the curve. The K(app)s for lacidipine and three other DHPs (nifedipine, nitrendipine and amlodipine) have been compared to pA2 values obtained from displacement of calcium concentration-response curves. In both REA and RBA the K(app)s for the four DHPs were not significantly different compared to their pA2s. The pK(app) values for lacidipine were estimated as 9.80 for REA and 10.20 for RBA.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester