Effects of spiroglumide, a gastrin receptor antagonist, on acid secretion in humans

Background A gastrin receptor antagonist, CR2194 (spiroglumide), was used to explore the physiological role of gastrin in regulating gastric acid secretion in humans. Materials and methods The effect of CR2194 on inhibition of gastrin-stimulated acid output was evaluated in a four-period crossover study. Each subject received intravenous doses of 1, 2.5 or 7.5 mg kg(-1) h(-1) CR2194 or saline (control) followed by graded increasing doses of gastrin (6.4-800 pmol kg(-1) h(-1)). Secondly, the effect of CR2194 on meal-stimulated intragastric acidity was evaluated by infusing either saline (control) or CR2194 (7.5 mg kg(-1) h(-1)) before and after food ingestion. Results Acid secretion was dose-dependently inhibited by CR2194. With CR2194, acidity was significantly reduced in the pre-meal and post-prandial period (P < 0.01 and 0.002 respectively), and the integrated gastrin response was augmented to 8.0 +/- 1.4 ng mL(-1) 240 min compared with 1.5 +/- 0.8 ng mL(-1) 240 min in the control experiment (P < 0.01). Finally, acid secretion in response to sham feeding was significantly reduced: 15.9 +/- 0.9 mmol 90 min(-1) in the control experiment compared with 2.8 +/- 0.9 mmol 90 min(-1) during CR2194 infusion (P < 0.05). Conclusion Gastrin receptor blockade with CR2194 alters gastric acid secretion in response to food ingestion or to sham feeding. The results support a physiological role for gastrin in regulating acid secretion in humans.