title: Calcium-agonists.
abstract: In contrast to nifedipine-like calcium antagonists, calcium agonistic 1,4-dihydropyridines have vasoconstricting and positive inotropic properties. BAY K 8644 has become the prototype of this new class. Its enantiomers show opposite effects on the calcium channel: one acts as a calcium agonist with the pharmacological profile of the racemic compound, its antipode has calcium antagonistic effects at 10 times higher concentrations. Voltage clamp studies reveal calcium current increasing effects at 3 X 10(-8) mol/l BAY K 8644, while the current is reduced at 3 X 10(-6) mol/l. Analysis of the calcium current activation and deactivation kinetics shows that BAY K 8644 leaves the mean closed times of the calcium channel unchanged while it increases the mean open times. From these data a reaction model of drug action is derived, suggesting that BAY K 8644 binds only to the open state of the Ca-channel.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; D014662:Vasoconstrictor Agents; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium