| Abstract: | The influence of methyl esterification of the carboxyl group of PGE1 on the gastric antisecretory and antiulcer activities were studied. The gastric antisecretory effects of PGE1 free acid and PGE1 methyl ester (PGE1ME) were studied in the Heidenhain pouch dog. Secretion was stimulated with constant intravenous infusion of histamine dihydrochloride. When a steady-state plateau of gastric secretion had been reached, the prostaglandins were administered either by a single intravenous bolus (10.0 mug/kg) or by continuous infusion (1.0 mug/kg/min). PGE1ME was found to be slightly more potent and longer-acting than PFE1 when administered by a single i.v. bolus. PGE1ME was also shown to be more potent than PGE1 when infused intravenously for a two-hour period. PGE1ME caused a significant alteration in gastric juice concentration of hydrogen and sodium ions in an inverse relationship. Potassium and chloride concentration were not altered from pre-existing steady-state values following administration of either form of prostaglandin. Similarly, PGE1ME was also found to possess significantly greater antiulcer activity in the rat forced-exertion ulcer test. These findings support the hypothesis that methyl esterification of the prostaglandin molecule will increase some of the biological actions of PGE1 through inhibition of metabolic beta-oxidation of the carboxylic side chain. |
