SR 33557, a Novel Calcium Entry Blocker. I. In Vitro Isolated Tissue Studies1

The effects of SR 33557 on isolated cardiovascular preparations were compared to those of nifedipine, verapamil and diltiazem. In rat aortic strips, SR 33557, like nifedipine, verapamil and diltiazem, caused a significant and simultaneous inhibition of potassium-Induced Ca influx and contractile responses (ni-fedipine> SR 33557> verapamil> diltiazem). SR 33557 also antagonized Ca-induced contractions in K’-depolaiized aorta preparations (pA2: 9.08 ± 0.03) and is the first calcium channel antagonist, structurally not related to 1,4-dihydropyridines, to inhibit competitively contractions induced by BAY K8644. In spike-generating vascular smooth muscle (rat portal vein), con-tractures evoked by noradrenafine (4 M) or KCI (1 00 mM) were reduced by all four antagonists, the pharmacological potency being nifedipine> SR 33557> verapamil> diftiazem. Wlike S