Studies on the possible mechanism of morphine-induced potentiation of the gastroulcerogenic effect of indomethacin in rats.

Morphine has been shown to produce a significant potentiation of indomethacin-induced gastric lesions in rats. The exact mechanism of this response has still not been worked out. Hence, in the present study, the effects of pirenzepine, cimetidine, disodium cromoglycate, OKY-046 (a thromboxane A2 synthesis inhibitor), BM 13.177 (a thromboxane A2 receptor antagonist), FPL 55712 (a leukotriene C4 antagonist) and a synthetic trimethylprostanoid, Ro 22-6923 have been studied on the gastric ulcers produced by indomethacin and its combination with morphine in rats. Only naloxone, FPL 55712 and Ro 22-6923 significantly reduced the morphine-potentiated ulcerogenic response of indomethacin as compared to the indomethacin ulcers in the groups pretreated with these drugs. It is, therefore, proposed that the potentiating effect of morphine is mediated through the opiate receptors, which, in some way, increase leukotriene C4 and decrease prostaglandin-like activities in the gastric mucosa. Further studies on the levels of leukotriene C4 and endogenous prostaglandins are suggested to substantiate these findings.