Differences Between the Effects of Calcium Antagonists in the Pithed Rat Preparation

Abstract

The drugs classed as calcium antagonists display marked differences in vitro and it has been proposed that different subclasses of antagonists exist (Spedding M. Nannyn Schmiedebergs Arch Pharmacol 1982; 318:234–40). The effects of these drugs have now been compared in vitro using the pithed rat preparation. Whereas the hypertensive effects of verapamil (0.1–3 μmol/kg i.v.(and diltiazem (0.1–10 μmol/kg i.v.) were accompanied by prolongation of PR intervals and second-degree atrioventricular block with little bradycardia, fendiline (0.1–30 μmol/kg i.v.), cinnarizine (0.1–10 μmol/kg i.v.), and pimozide (0.1–10 μmol/kg i.v.) reduced heart rate at hypoterisive doses hut 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 μmol/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.