Aims: 

Actions of capsaicin (given in stimulatory doses), atropine, omeprazole, famotidine, ranitidine, cimetidine have been compared by molecular-pharmacological methods on gastric acid secretion and gastric mucosal damage.

Methods: 

Dose-response curves were identified on gastric acid secretion of 4-h pylorus-ligated rats, gastric basal acid secretion of humans and on the gastric mucosal damage induced by different chemicals. The necessary doses producing 50% inhibition in gastric acid secretion and gastric mucosal damage were calculated in molar values/kgBW. The drugs were given subcutaneously or via intragastric administration. The values of affinity (pD) and intrinsic activity curves (a-values) were calculated. The values of the pD₂ (necessary dose to inhibit gastric acid secretion and gastric mucosal damage by 50%) and the intrinsic activity to produce 50% decrease (pA₂) in both parameters were calculated from the affinity and intrinsic activity curves. The intrinsic activity of atropine(a) was taken as 1.00 for comparing the effects of chemicals on acid secretion and mucosal damage.

Results: 

1. The pD₂ values for drugs inhibiting gastric acid secretion in 4-h pylorus-ligated rats were: capsaicin:8.48; atropine:5.75; omeprazole:4.88; cimetidine:3.00. Similar values for gastric basal acid output in humans were: capsaicin:5.88; atropine:5.40; cimetidine:2.23; famotidine:3.77; omeprazole:3.97. 2. The intrinsic activities were: capsaicin:0.76; atropine:7.44; omeprazole:1.00; cimetidine:1.00 in 4-h pylorus-ligated rats, while these values were: capsaicin:0.76; atropine:1.00; omeprazole:1.00;cimetidine:1.00; famotine:1.00; in human gastric basal acid outputs:1.00; 3. The pA₂ values were: capsaicin: 8.50; atropine:5.80; omeprazole:4.90; famotidine:3.70; cimetidine:3.20 for drugs inhibiting gastric mucosal damage in rats. These values in humans after indomethacin- or ethanol-induced gastric mucosal damage were: capsaicin:5.87; atropine:5.40; omeprazole:3.97; famotidine:3.77 and cimetidine:2.23.

Conclusion: 

These results suggest essential physiological regulatory roles of capsaicin-sensitive vagal afferent nerves involved in the regulation of gastric acid secretion in gastric mucosal protection in both animal experiments and in humans. Application of small doses of capsaicin may represent a new therapeutic pathway in this field.