Interactions of cimetidine and pirenzepine on peptone-stimulated gastric acid secretion in man.

Combinations of H2-receptor antagonists and classical anticholinergics inhibit stimulated gastric acid secretion more than either drug alone. In double blind, placebo controlled, randomised studies we have compared the effects of single and combined intravenous bolus injections of cimetidine and pirenzepine on peptone-stimulated acid secretion and serum gastrin in man. Combined injection of 3.0 mg/kg cimetidine and 0.3 mg/kg pirenzepine suppressed stimulated acid secretion significantly more than either drug alone, and by 90% in healthy volunteers (n = 8) and patients with duodenal ulcer (n = 5). Side-effects (prolactin stimulation, blurred vision) were diminished by reducing the combined dosages to 1.5 mg/kg cimetidine, to 0.075 and 0.15 mg/kg pirenzepine in another series (n = 10). Postprandial gastrin was not affected by any combination. Combination of cimetidine and pirenzepine suppress food-stimulated gastric secretion more effectively than combination of H2-blockers with classical anticholinergics. Pirenzepine--unlike classical anticholinergics--may distinguish between different subclasses of muscarinic receptors and have a more selective antimuscarinic action. Its interaction with H2-receptor antagonists on parietal cell function seems to be synergistic. Such a combination could be of advantage in patients with gastrinoma, in patients with ulcers and hypersecretion resistant to single drug treatment, and in critically ill patients as prophylaxis of stress ulcer bleeding.