GASTRIC ANTISECRETORY AND ANTIULCER PROPERTIES OF PGE2, 15-METHYL PGE2, AND 16,16-DIMETHYL PGE2 - INTRAVENOUS, ORAL AND INTRAJEJUNAL ADMINISTRATION

  • 1 January 1976
    • journal article
    • research article
    • Vol. 70  (3) , 359-370
Abstract
15-Methyl prostanglandin (PG)E2 and 16,16-dimethyl PGE2 were 40 and 100 times, respectively, more potent than PGE2 after i.v. administration in inhibiting histamine-stimulated gastric secretion in dogs with a denervated (Heidenhain) gastric pouch; and were active orally and intrajejunally, whereas PGE2 was inactive and exerted antisecretory activity for longer duration than PGE2. 16,16-Dimethyl PGE2 was about 2.5 times more potent than 15-methyl PGE2. Volume, acid concentration and output and pepsin output (but not concentration) were reduced in a dose-dependent manner. In the rat 16,16-dimethyl PGE2 inhibited gastric secretion and prevented ulcer formation produced by various methods: gastric ulcers (Shay, and steroid induced) and duodenal ulcers (secretogogue induced). In this species 16,16-dimethyl PGE2 was 2-50 times more potent than PGE2, depending on the endpoint and was active orally. These prostaglandins appear to inhibit gastric acid secretion by acting directly on the parietal cells, making these unresponsive to most stimulants. Vomiting was a side effect of the prostaglandin analogues in the dog but almost exclusively when there were given orally. After i.v. or intrajejunal administration at doses inhibiting gastric secretion by 80%, vomiting was seen only once. 15-Methyl PGE2 and 16,16-dimethyl PGE2 may be of value in the treatment of peptic ulcer.