A unitary mechanism of calcium antagonist drug action.
[3H]Nitrendipine binding to drug receptor sites associated with calcium channels is allosterically regulated by a diverse group of calcium channel antagonists. Verapamil, D-600 (methoxyverapamil), tiapamil, lidoflazine, flunarizine, cinnarizine, and prenylamine all reduce [3H]nitrendipine binding affinity. By contrast, diltiazem, a benzothiazepine calcium channel antagonist, enhances [3H]nitrendipine binding. All these drug effects involve a single site allosterically linked to the [3H]nitrendipine binding site. Inhibition of [3H]nitrendipine binding by prenylamine, lidoflazine, or tiapamil is reversed by D-600 and diltiazem, which alone respectively slightly reduce or enhance [3H]nitrendipine binding. Diltiazem reverses the inhibition of [3H]nitrendipine binding by D-600. Our prediction that drugs allosterically regulating [3H]nitrendipine binding should be calcium antagonists is confirmed by calcium antagonism in guinea pig ileum observed with the antihistamine dimethindene, the neuroleptics thioridazine and mesoridazine, and the anticholinergic biperiden.
D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000145:classification* / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D007700:Kinetics; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine
D002121:Calcium Channel Blockers; D009568:Nitrendipine; D009543:Nifedipine