Cytoprotective and antisecretory properties of a non-diarrheogenic and non-uterotonic prostacyclin analog: U-68, 215

Abstract

U-68,215 [15-Cyclohexyl-9-deoxo-13, 14-dihydro-2′, 9a-methano-4,5,6,16,17,18,19,20-octanor-3-oxa-3,7-(′1,′3-interphenylene)-PGE 1] is a stable prostacyclin analog. When given orally to rats, it is cytoprotective for the stomach (ED 50: 0.8 μg/kg) and the intestine (ED 50: 22 μg/kg), is gastric antisecretory (ED 50: 35 μg/kg) and antiulcer (aspirin) (ED 50: 5 μg/kg). The oral antisecretory ED 50 in dogs in 50 μg/kg. It has a long duration of gastric cytoprotection: 8–10 hours compared to 3 hours for 16, 16-dimethyl PGE 2 Unlike most prostaglandins of the E type, it is not diarrheogenic (not enteropooling), it does not induced cellular proliferation of the gastroeintestinal mucosa, when given twice a day for eight days, it is not uterotonic (in monkeys), and it does not prevent embryo implantation in hamsters. It ihibits ex vivo platelet aggregation (ED 50: 300 μg/kg), but does not promote bleeding from cut vessels nor from gastric ulcers. U-68,215 lowers blood pressure at a n oral dose correponding to 1–5 time the antisecretory ED 50 in rats and dogs, and to 150 times the cytoprotective ED 50 in rats. It may be of therapeutic value in the treatment of conditions where inhibition of gastric acid secretion is desirable, e.g., gastric and duodenal ulcer, and in conditions responding to cytoprotection, e.g., stress ulcers, hemorrhagic gastritis and gastric erosions associated with nonsteroidal antiinflammatory drugs.