<正> Aim:To evaluate the analgesic effects of 2 celecoxib derivatives and their inhibi-tory effects on cyclooxygenase（COX）.Methods:Four antinociceptive assayswere used:the acetic acid-induced writhing test,hot plate test,hot tail-flick testand formalin test.Three doses were used in the analgesic assays and ED50valueswere calculated.For the selectivity assay,macrophages were incubated with testcompounds at various concentrations and then stimulated with calcimycin orlipopolysaccharide（LPS）.The amounts of 6-keto-prostaglandin F1α(6-keto-PGF1α)and prostaglandin E2（PGE2）in the supernatant were examined by radioimmunoas-say（RIA）.The selectivity of the test compounds was expressed as the IC50.COX-1/IC50.COX-2value.Results:Celecoxib and its 2 derivatives had a significant analge-sic effect.The ED50values of celecoxib,PC-406 and PC-407 were 94.2,67.9,and 63.3mg/kg,respectively,for the acetic acid-induced writhing test;104.7,89.1,and 30.0mg/kg,respectively,for the hot tail-flick response test;60.7,56.7,and 86.2 mg/kg,respectively,for the hot plate response test;67.1,55.8,and 68.8 mg/kg,respectively,for the formalin-induced response.That is,the EDs0 of PC-406 was the lowest forthe formalin and hot plate tests,which focus on changes above the spinal cordlevel;however,the EDs0 of PC-407 was lowest for the tail-flick and writhing tests,which focus on changes at the spinal cord level.Celecoxib and PC-407 inhibitedCOX-1 with IC50values of 39.8 and 27.5 nmol/L,respectively.PC-406 inhibitedCOX-1 with an IC50value of more than 1000 nmol/L.The IC50values for the effectof celecoxib,PC-406 and PC-407 on COX-2 were 4.8,8.9,and 1.9 nmol/L respectively.The IC50.COX-1]IC50.COX-2ratios for celecoxib and PC-407 were 8.3 and 14.4,respec-tively.For PC-406,the ratio was greater than 112.2.Conclusion:Derivatives ofcelecoxib via substitution with an isopropyl or naphthyl group at the 5 position inthe pyrazole ring still have analgesic effects and the ability to selectively inhibitCOX-2.Substitution with a naphthyl group may have more effect on the periph-eral pain pathway,whereas substitution with an isopropyl group may have moreeffect on the central pain pathway.This phenomenon occurs partly becausesubstitution with an isopropyl group is more beneficial for COX-2 selectivity thanis substitution with a naphthyl group.
