Gastric histamine content and gastric ulcer formation in cold/restraint stressed rats: Effects of cinnarizine and flunarizine

The effects of the calcium channel blockers cinnarizine (20 mg/kg p.o.) and flunarizine (10 mg/kg p.o.) on gastric and small intestine histamine content and ulcer formation were determined in cold/restraint stressed rats (4°C for 3 h). The effects of cimetidine (100 mg/kg p.o.) were studied for comparison. After the stress, a significant increase (+27%) in gastric histamine content concomitant with gastric ulceration was observed. Pretreatment with cinnarizine or flunarizine restored histamine to the control value and reduced both the incidence (–22% and –44% respectively) and the severity (-nearly 35%) of gastric ulcers. Neither marked changes in histamine content nor mucosal lesions were detected in the small intestine. The effects of cinnarizine and flunarizine resembled those of cimetidine. The obtained data suggest a possible relation between the decrease in the elevated histamine content in stressed rats and the protection against ulcer formation exerted by cinnarizine and flunarizine.