Pharmacological properties of Ciloprost, a stable prostacyclin analogue, on the gastrointestinal tract.
The effect of Ciloprost on the gastrointestinal tract was studied in rats and compared with prostacyclin (PGI2) and/or PGE2. In the anaesthetized rat continuous i.v. infusion of Ciloprost decreased pentagastrin stimulated gastric acid secretion with the same potency [ED 50 -35 micrograms/(kg x h)]as PGI2 [ED 50 -42 micrograms/(kg x h)]. In the pylorus-ligated rat Ciloprost reduced acid secretion with an ED50 of about 6.4 mg/kg p.o. whereas PGE2 and PGI2 were ineffective during submaximal stimulation of acid secretion by pentagastrin. In the same experimental design continuous i.v. infusion of Ciloprost and PGI2 caused 50% reduction in gastric acid output with doses of 80 and 24 micrograms/(kg x h), respectively. Ciloprost prevented indomethacin-induced gastric erosions at an ED50 of 60 micrograms/kg p.o., compared to 10 micrograms/kg p.o. of PGE2, whereas PGI2 showed only weak cytoprotective activity. The stable prostacyclin analogue inhibited castor oil induced enteropooling with a 4-5 fold higher potency than PGI2 and delayed castor oil induced diarrhoea more effectively than its natural counterpart. Intestinal motility was strongly reduced by both PGI2 and Ciloprost. Gastric emptying was also reduced after PGI2 and Ciloprost administration, with a 4-5 fold higher activity of the stable analogue. The present results demonstrate, that Ciloprost shows a biological profile similar to that of PGI2.
D000818:Animals; D004064:Digestive System / Q000187:drug effects*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D016285:Iloprost; D007213:Indomethacin / Q000037:antagonists & inhibitors; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011458:Prostaglandins E; D011464:Epoprostenol; D016285:Iloprost; D015232:Dinoprostone; D007213:Indomethacin