Synergistic actions of propantheline bromide with cimetidine and thiopropazate hydrochloride in the prevention of stress ulcer formation in rats.

The effects of propantheline bromide (PB), cimetidine (CM) and thiopropazate hydrochloride (TP) on the course of stress ulcer formation were investigated. Gastric ulcers were induced by subjecting rats to forced exertion. Intragastric administration of PB, CM or TP produced dose-dependent inhibition of gastric ulceration with parallel dose-response curves. PB was found to be 10 times more potent than TP and 44 times more potent than CM. Administration of subtherapeutic doses of PB and TP in combination produced significant synergistic antiulcer activity. Similarly, PB significantly potentiated the antiulcer actions of CM. However, TP in combination with CM showed no more than simple additive effects. The basis for these enhanced antiulcer activities is not fully understood, but they may be related to suppression by PB of one or more factors in the pathophysiology of stress ulcer formation separate from those affected by TP and CM. This finding supports the concept that a combination of anticholinergic drugs with either histamine H2 antagonists or with tranquilizers may be very useful in the prevention of stress ulcer disease in man.