Findings in gastric mucosa and gastric secretion of methyl O-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) and reserpine derivatives administered subcutaneously to rats.

Abstract

CD-3400 developed by Nippon Chemiphar Co. Ltd., is a new antihypertensive agent belonging to the class of rauwolfia alkaloids. Influence of the agent on gastric mucosa, healing process of acetic acid-induced gastric ulcer and gastric juice in rats was investigated and compared with effects of reserpine and rescinnamine. CD-3400-induced gastric lesions were fewer in number than those produced with reserpine and rescinnamine in fasted rats. After a three day treatment of CD-3400 to fed rats, however, there were few gastric lesions, while reserpine and rescinnamine-induced gastric lesions were aggravated to a greater extent than when a single administration was given to fasted rats. Influence of CD-3400, reserpine and rescinnamine on the healing process of acetic acid-induced ulcer was insignificant, but treatment with high doses of reserpine and rescinnamine resulted in death. Pretreatment with CD-3400 and reserpine produced a decrease in gastric acid and K⁺, and an increase in Na⁺. Repeated administration of reserpine for 5 days resulted in a decrease of both gastric volume and acid, while such was not seen with CD-3400. Treatment with anticholinergic agents such as atropine sulfate and atropine methylbromide inhibited CD-3400 and reserpine-induced gastric lesions. From these results, it would appear that cholinergic factors play a role in the pathogenesis of CD-3400-induced gastric lesions, as is the case with reserpine, and that the responses of these lesions to reserpine and CD-3400 correlate with changes of ionic fluxes in gastric juice.