[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.

Original languageEnglish
Pages (from-to)860-864
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3 I
StatePublished - 1983


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