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  • Title: Cytoprotective and antisecretory properties of a non-diarrheogenic and non-uterotonic prostacyclin analog: U-68,215.
    Author: Robert A, Aristoff PA, Wendling MG, Kimball FA, Miller WL, Gorman RR.
    Journal: Prostaglandins; 1985 Oct; 30(4):619-49. PubMed ID: 4081062.
    Abstract:
    U-68,215 [15-Cyclohexyl-9-deoxo-13,14-dihydro-2',9 alpha-methano-4,5,6,16,17,18,19,20-octanor-3-oxa-3,7-(1', 3'-interphenylene)-PGE1] is a stable prostacyclin analog. When given orally to rats, it is cytoprotective for the stomach (ED50: 0.8 micrograms/kg) and the intestine (ED50: 22 micrograms/kg), is gastric antisecretory (ED50: 35 micrograms/kg) and antiulcer (aspirin) (ED50: 5 micrograms/kg). The oral antisecretory ED50 in dogs is 50 micrograms/kg. It has a long duration of gastric cytoprotection: 8-10 hours compared to 3 hours for 16,16-dimethyl PGE2. Unlike most prostaglandins of the E type, it is not diarrheogenic (not enteropooling), it does not induce cellular proliferation of the gastrointestinal 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 inhibits ex vivo platelet aggregation (ED50: 300 micrograms/kg), but does not promote bleeding from cut vessels nor from gastric ulcers. U-68,215 lowers blood pressure at an oral dose corresponding to 1-5 times the antisecretory ED50 in rats and dogs, and to 150 times the cytoprotective ED50 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.
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