A comparison of pirenzepine and cimetidine inhibition of centrally-mediated gastric acid and pepsin secretion in the gastric-fistula cat.

The effects of pirenzepine, a muscarinic antagonist, and cimetidine, a histamine H2-receptor antagonist, on 2-deoxy-D-glucose-stimulated gastric secretion were investigated in the gastric-fistula cat. Both drugs inhibited gastric acid secretion in a dose-related manner; the oral ED50 of pirenzepine was 0.37 (0.22-0.59) mg/kg and cimetidine was 4.6 (3.3-5.8) mg/kg. The two drugs affected pepsin secretion in characteristically different ways. The inhibition of pepsin secretion by cimetidine was small and inconsistent when compared with the effect on acid. Throughout the dose-range cimetidine tended to reduce volume more than pepsin secretion. The resulting rise in concentration of pepsin suggested that cimetidine had an indirect effect on pepsin secretion. In contrast, pirenzepine exerted a direct effect on both acid and pepsin. Hence at doses producing a 50% inhibition of acid secretion pirenzepine and cimetidine reduced pepsin secretion by 78% and 25% respectively. These observations were consistent with the concept that muscarinic receptors and not histamine H2-receptors are involved in the regulation of pepsin secretion.