A possible approach to the suppression of side effects induced by PGE1.

Prostaglandin E1 (PGE1) is known to possess various actions in vivo. Of these actions, the contraction of the ileum and inflammation are undesirable side effects. We previously proposed a hypothesis concerning the receptors for human blood platelet aggregation and its inhibition, and the contraction of the ileum and uterus based on a study of structure-activity relationships. If the same principle can be applied to contraction of the ileum and inflammation induced by PGE1, compounds that suppress the side effects of PGE1 can be developed. The antihistamine diphenylpyraline and the anticholinergic atropine antagonized PGE1-induced contraction of the ileum in guinea pigs. Papaverine, which is a smooth muscle relaxant, also acted as an antagonist. Gabexate mesylate (FOY), a non-peptide proteinase inhibitor, inhibits guinea pig ileum contraction induced by PGE1, but epsilon-guanidinocaproic acid (GCA), a metabolite of FOY, does not. Increased microvascular permeability of the abdominal skin in rats induced by the local injection of PGE1 and histamine was suppressed by atropine, papaverine and diphenylpyraline. FOY, not GCA, had a weak inhibitory action. We demonstrate the possibility of suppressing the side effects of PGE1 based on the results obtained in the present and previous studies.