Abstract

2,2'-Bipyridine (CI-588) was evaluated for gastric antisecretory and other pharmacologic activities. It decreased secretion volumes and hydrogen ion and pepsin outputs in the 4-hrpylorus-ligated rat. It reduced food-stimulated secretion volumes and hydrogen ion outputs in dogs with innervated gastric pouches. At dose levels tested, CI-588 had no significant effect on insulin- or histamine-stimulated secretions in the dog. CI-588 reduced stress-induced gastric lesions in rats, antagonized histamine-induced gastric lesions in guinea pigs, but had minimal effect against polymyxin B-induced gastric lesions in rats. CI-588 had no effect on acetylcholine-and dimethylphenylpiperazinium iodide-induced blood pressure changes in the dog or on methacholine-induced chromodacryorrhea in the rat. It showed no mydriatic activity in the rat. It is concluded that CI-588 gastric antisecretory activity is due to action on mechanisms other than those of the cholinergic system. Reserpine antagonism of CI-588 antisecretory activity in rats was partially reversed by dl-3,4-dihydroxyphenylalanine and 5-hydroxytryptophan (5-HTP). Epinephrine and norepinephrine effects on dog blood pressure were partially antagonized by high doses of CI-588. This suggests that the sympathetic and possibly the serotonergic systems are involved in the activity of CI-588.