fce-20700 and Stomach-Ulcer

Different doses of the new chemically stable PGE2 analogue, FCE 20700, (150, 300, 450, 900, 1200 and 1800 micrograms kg-1) and of 16,16-dimethyl PGE2, DMPGE2, (1, 3, 10, 30 and 100 micrograms kg-1) were administered by gavage to pylorus-ligated rats. The dose-response relationship in preventing gastric mucosal damage and in inhibiting gastric acid and pepsin secretion was investigated. In the same animals, a simultaneous evaluation of barrier and luminal mucus was also performed. Both compounds were markedly active in preventing the macroscopic damage of the gastric mucosa and, at higher doses, in inhibiting gastric acid secretion. FCE 20700 was approximately 100-150 times less potent than DMPGE2. Mucosal protection appeared to be exerted by the two prostaglandins independently of any action on mucus. Furthermore, as the antisecretory doses were approached, a decline in protective activity became evident, suggesting that the dosage of prostaglandins is critical, making it possible to orient their activity either towards mucosal protection or towards acid inhibition.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Dinoprostone; Dose-Response Relationship, Drug; Female; Gastric Acid; Gastric Mucosa; Mucus; Pepsin A; Prostaglandins E, Synthetic; Pylorus; Rats; Rats, Inbred Strains; Reference Values; Stomach Ulcer

A new, chemically stable analogue of PGE2, 11-deoxy-13,14-didehydro-16(S)-methyl PGE2 methylester (FCE 20700) was studied for the prevention of different gastrointestinal ulcers and for the inhibition of basal gastric acid secretion in the rat. The diarrhoea-inducing activity was also investigated. FCE 20700 was more potent than PGE2 in the prevention of stress-induced gastric ulcers (ED50 = 262 and 787 mcg/kg) and indomethacin-induced intestinal ulcers (ED50 = 557 and 4569 mcg/kg), and showed the same potency as PGE2 in the prevention of ethanol (ED50 = 9.2 and 14.8 mcg/kg) and indomethacin-induced gastric ulcers (ED50 = 37.8 and 22.3 mcg/kg). FCE 20700 weakly affects gastric acid secretion with an ED50 of 2385 mcg/kg, showing clear separation of antisecretory activity and gastric antiulcer potency. FCE 20700 does not induce diarrhoea in rats at doses up to 6.25 mg/kg, 10 to 600 times the effective antiulcer doses.

Topics: Animals; Anti-Ulcer Agents; Diarrhea; Dinoprostone; Ethanol; Gastric Juice; Indomethacin; Intestines; Male; Peptic Ulcer; Prostaglandins E, Synthetic; Rats; Secretory Rate; Stomach Ulcer; Stress, Physiological

A study was made of the interaction between FCE 20700 (11-deoxy-13,14-didehydro-16(S)-methyl-PGE2 methylester) at a fixed dose of 250 mcg/kg and the ulcerogenic and antiinflammatory effect of indomethacin (I) on rat carrageenin paw edema. The combination tested showed the same antiinflammatory effect as I alone: potency ratio FCE 20700 + I/I was 1.03, demonstrating the lack of interaction between the two compounds. Moreover the gastric lesions in FCE 20700 + I treated rats were markedly reduced, allowing the dosage of I to be increased by about three times without increasing its ulcerogenic effect.

Topics: Animals; Dinoprostone; Drug Interactions; Gastric Mucosa; Indomethacin; Male; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer