PMID: 2481028Dec 1, 1989Paper

Anti-ischemic and vasorelaxant effects of the new benzazepine calcium channel blocker SQ 31,765.

The Journal of Pharmacology and Experimental Therapeutics
G J GroverS Moreland

Abstract

The anti-ischemic effects of SQ 31,765 or its relatively inactive enantiomer SQ 32,189 (to test for effects not related to calcium channel blockade) were determined in a model of stable angina. Anesthetized dogs were given saline (n = 6), SQ 31,765 (n = 6; 0.2 mg/kg) or SQ 32,189 (n = 6; 0.2 mg/kg) i.v. 10 min before ischemia. The effect on pacing-induced ST-segment elevation (pacing + left anterior descending coronary artery stenosis) and myocardial blood flow were determined. SQ 31,765 reduced ST-elevation (P less than .05) compared to saline at 10, 40 and 70 min after infusion (5.9 +/- 1.4 and 12.0 +/- 1.4 mV, respectively, at 70 min). SQ 32,189, which is a 10-fold less potent calcium channel blocker in coronary arteries, did not affect ST-elevation (11.8 +/- 2.1 mV). Left anterior descending coronary artery stenosis during atrial pacing resulted in a significant reduction in subendocardial flow in all groups before drug infusion (41 +/- 7, 44 +/- 7 and 35 +/- 9 ml/min/100 g for saline, SQ 31,765 and SQ 32,189, respectively) and treatment with SQ 31,765 did not affect this flow. SQ 32,189 further reduced subendocardial blood flow such that it was significantly lower compared to saline. To test for any partial agonist activit...Continue Reading

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