Differences between the effects of calcium antagonists in the pithed rat preparation

The drugs classed as calcium antagonists display marked differences in vitro and it has been proposed that different subclasses of antagonists exist (Spedding M. Naunyn Schmiedebergs Arch Pharmacol 1982; 318:234-40). The effects of these drugs have now been compared in vivo using the pithed rat preparation. Whereas the hypotensive effects of verapamil (0.1-3 mumol/kg i.v.) and diltiazem (0.1-10 mumol/kg i.v.) were accompanied by prolongation of PR intervals and second-degree atrioventricular block with little bradycardia, fendiline (0.1-30 mumol/kg i.v.), cinnarizine (0.1-10 mumol/kg i.v.), and pimozide (0.1-10 mumol/kg i.v.) reduced heart rate at hypotensive doses but had less marked effects on AV conduction, thus implying different selectivities among calcium antagonists for the sinus or AV nodes. These differences were not secondary to effects on the autonomic nervous system. In contrast, nifedipine (0.01-1 mumol/kg i.v.) had no effect on the ECG in doses which markedly reduced blood pressure elevated by an infusion of angiotensin II and thus showed specificity for vascular smooth muscle. The marked differences between the effects of the calcium antagonists in vivo confirm the disparate nature of this group of drugs. The reasons for these differences are discussed.