Molecular Pharmacological Approaches to Effects of Capsaicinoids and of Classical Antisecretory Drugs on Gastric Basal Acid Secretion and on Indomethacin-Induced Gastric Mucosal Damage in Human Healthy Subjects (Mini Review)

Imre      Laszlo Szabo; Jozsef      Czimmer; Janos      Szolcsanyi; Gyula      Mozsik

doi:10.2174/1381612811306010084

Abstract

Background: Actions of various drugs have been tested on the gastric acid basal secretion and on the drug (Indomethacin)- induced gastric mucosal damage; however their physiological and pharmacological mechanisms have not been compared. Aims: The effects of capsaicinoids, atropine, cimetidine, omeprazole, famotidine and ranitidine were studied on gastric basal acid output, whereas the gastric mucosal preventive effects of capsaicinoids (capsaicin), atropine and cimetidine were tested on the indomethacin-induced gastric mucosal microbleedings in human healthy subjects. Results were presented by molecular pharmacological method; affinity (pD) and intrinsic activity (α-values) were calculated. Intrinsic activity curves are based on comparison to atropine effect (α atropine= 1.00). For evaluation of physiological and pharmacological effects of compounds molar doses of pD2 (necessary doses to produce 50% inhibition) and pA2 (50% inhibion on intrinsic activity) were calculated from affinity and intrinsic activity curves. Results: The pD2 values for compounds were as follows: 5.88 for capsaicinoids, 5.40 for atropine , 2.23 for cimetidine, 3.33 for ranitidine, 3.77 for famotidine and 3.97 for omeprazole. α - value results for compounds were: 0.76 for capsaicinoids, and 1.00 for atropine, cimetidine, ranitidine, famotidine and omeprazole all equal to 1.00 on gastric acid basal secretion. The pD2 values on indomethacin-induced gastric mucosal microbleeding were found as follows: 6.00 for capsaicinoids, 5.50 for atropine, and 3.50 for cimetidine, meanwhile α-values resulted 0.76 for capsaicinoids, 1.00 for atropine and cimetidine. Conclusions: Comparison classical antisecretory drugs acting on different pathways but in much more higher molar concentrations. The atropine and capsaicinoids act in about the same molar concentration which suggests a significant physiological role for capsaicin sensitive afferent nerves in the regulation of gastric basal acid secretion and in the prevention of chemically- induced gastric mucosal protection in human healthy subjects, suggesting a novel physiological pathway in regulation. These results clearly indicate the molecular pharmacological backgrounds of actions of classical antisecretory drugs and physiological role of capsaicin- sensitive afferent nerves in human healty subjects on the gastric basal secretion and on the prevention of drug-induced gastric mucosal damage.

Keywords: Capsaicinoids, gastric acid inhibitory drugs, indomethacin-induced gastric mucosal damage, molecular pharmacology, physiological and pharmacological regulations of afferent and efferent vagal nerve, atropine, cimetidine, omeprazole, famotidine, anitidine