THE GASTRIC ANTIULCER ACTIVITY OF CHLORBENZOXAMINE, A NON-ANTICHOLINERGIC PIPERAZINE COMPOUND

¹ Department of Pharmacology, Warner-Lambert Research Institute, Morris Plains, New Jersey

Chlorbenzoxamine, a structural analogue of hydroxyzine, produces a unique antagonism of gastric ulceration induced in rats and dogs by various procedures. This effect is not accompanied by a significant gastric secretory depression or a reduction in gastric acid concentration as evaluated in the 4-hour pylorus-ligated rat. The optimal antiulcer dose in both species is less than 2 mg/kg and is critical for each ulcerogenic procedure. Doses higher than optimum are either less effective or are ulcerogenic.

Chlorbenzoxamine does not show anticholinergic or antihistaminic activity in vitro but does produce a nonspecific depression of isolated smooth muscle. This latter effect resembles that of papaverine both qualitatively and quantitatively. Intravenous administrations of 1, 5 or 10 mg/kg to anesthetized dogs induce brief and variable depressions of intestinal motility and an abrupt, transient vasodepression accompanied by a significant increase in pulse pressure and heart rate.

The antiulcer effect of chlorbenzoxamine in rats is abolished by hypophysectomy suggesting a central or endocrine mechanism of action. This possibility has been discussed.