Diltiazem-like effect of thioridazine on the dihydropyridine binding site of the calcium channel of rat myocardial membranes.
The phenothiazine thioridazine enhances the binding of [3H]-nitrendipine to cardiac membranes and antagonizes the inhibition of [3H]-nitrendipine binding by other classes of calcium channel blockers. These effects are similar to those of diltiazem. The increased binding of [3H]-nitrendipine in the presence of thioridazine or diltiazem is due to increased binding affinity rather than an increased number of binding sites. Increased affinity is due in part to a decrease in the dissociation rate of nitrendipine in the presence of either thioridazine or diltiazem. Thioridazine also reverses the blocking effect of tiapamil (a phenylalkylamine) on [3H]-nitrendipine binding to rat heart membranes, as does diltiazem, suggesting that thioridazine binds to the same site as diltiazem. Thioridazine may have calcium channel blocking effects in the high therapeutic and toxic dose ranges that could be responsible for some of its adverse cardiovascular effects.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D002462:Cell Membrane / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013881:Thioridazine / Q000494:pharmacology*
D001552:Benzazepines; D015220:Calcium Channels; D007473:Ion Channels; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D004110:Diltiazem; D009543:Nifedipine; D013881:Thioridazine; D002118:Calcium