Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats

In this study,the anti-inflammatory and anti-ulcerative effects of metyrosine,a selective tyrosine hydroxylase enzyme inhibitor,were investigated in rats. for ulcer experiments,indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. for these experiments,rats were fasted for 24 h. different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats,followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test,or 50% ethanol for the ethanolinduced test. results have shown that at all of the doses used (50,100 and 200 mg/kg),metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. in addition,to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (cox) activity in inflammatory tissue (rat paw). the results showed that all doses of metyrosine significantly inhibited high cox-2 activity. the degree of cox-2 inhibition correlated with the increase in anti-inflammatory activity. in conclusion,we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of cox-2 enzymes by metyrosine. we also found that adrenalin levels are reduced upon metyrosine treatment,which may be the cause of the observed gastro-protective effects of this compound. © 2010 by institute of pharmacology polish academy of sciences.