Nocloprost, a unique prostaglandin E 2 analog with local gastroprotective and ulcer-healing activity

Abstract

Nocloprost (9β-chloro-16,16-dimethyl prostaglandin E 2 (PGE 2)) was examined for gastroprotective and ulcer-healing activity and compared to 16,16-dimethyl PGE 2 (dmPGE) in rats. Nocloprost given intragastrically (i.g.) at various doses (0.01–10 μg/kg) 30 min before 100% ethanol, acidified aspirin (ASA), acidified taurocholate, water immersion, or restraint stress dose dependently prevented the formation of gastric lesions, the ID 50 values being 0.25, 0.58, 0.06 and 0.12 μg/kg. respectively. The gastroprotection provided by nocloprost given i.g. was somewhat enhanced by the presence of acid in the stomach and was reduced by inhibition of gastric acid secretion. Nocloprost given s.c. also showed protective activity against ethanol damage but was ineffective when applied intraduodenally. The protective effect of nocloprost lasted about 8 h whereas that induced by dmPGE lasted 6 h. Nocloprost (0.01–100 μg/kg) given i.g. failed to affect gastric acid secretion or intestinal secretion (enteropooling) but prevented the increased gastroduodenal alkaline secretion. Nocloprost alone caused only a transient increase in the mucosal blood flow but prevented the fall in blood flow caused by 100% ethanol. [ 3H]Nocloprost was absorbed from the small intestine but was then taken up and metabolized by the liver and excreted into the bile so that very little reached the systemic circulation in an unchanged form. Nocloprost, unlike dmPGE, accelerated the healing of chronic gastric ulcerations and enhanced mucosal growth. We conclude that nocloprost is a locally active PGE 2 analog with high cytoprotective and ulcer-healing efficacy.