Ethenzamide Exerts Protective Effects against Ibuprofen-Induced Gastric Mucosal Damage in Rats by Suppressing Gastric Contraction

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage, in which gastric hypermotility has been reported to play a primary role. The antipyretic analgesic drug ethenzamide (ETZ) is widely used in combination with other NSAIDs and, in a recent study, was found to possess 5hydroxytriptamine (5HT) 2B receptor antagonistic activity. Therefore, the inhibition of gastric contraction via 5HT 2B receptor blockade by ETZ might contribute to ETZ's protective effect against NSAIDs-induced gastric mucosal damage. In the present study, we examined the effects of ETZ on gastric contraction and ibuprofen (IBP)-induced gastric mucosal damage in rats. We found that ETZ suppressed both 5HT-and α-methyl-5HT (5HT 2 receptor agonist)-induced contractions of rat-isolated gastric fundus in a concentration-dependent manner. This suppressive effect of ETZ was not seen for either high-KCl-or acetylcholine-induced contractions. Furthermore, ETZ was confirmed to decrease ibuprofen-induced gastric mucosal damage in a dosedependent manner in rats. Similarly, clonidine is known to reduce gastric motility, and methysergide (a 5HT 2 receptor antagonist) is known to inhibit 5HT-induced contractions of the gastric fundus, which also decreases IBP-induced gastric mucosal damage, respectively. Although further research on other possible sites or mechanisms of action would be needed, these results suggest that ETZ exerts a protective effect against IBPinduced gastric mucosal damage and that suppressing the gastric contraction may play an important role in the gastroprotective effect of ETZ.