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 ED_(50)valueswere 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 F_(1α)(6-keto-PGF_(1α))and prostaglandin E_2(PGE_2)in the supernatant were examined by radioimmunoas-say(RIA).The selectivity of the test compounds was expressed as the IC_(50.COX-1)/IC_(50.COX-2)value.Results:Celecoxib and its 2 derivatives had a significant analge-sic effect.The ED_(50)values 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 IC_(50)values of 39.8 and 27.5 nmol/L,respectively.PC-406 inhibitedCOX-1 with an IC_(50)value of more than 1000 nmol/L.The IC_(50)values for the effectof celecoxib,PC-406 and PC-407 on COX-2 were 4.8,8.9,and 1.9 nmol/L respectively.The IC_(50.COX-1)]IC_(50.COX-2)ratios 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. Aim: To evaluate the analgesic effects of 2 celecoxib derivatives and their inhibi-tory effects on cyclooxygenase (COX). Methods: Four antinociceptive assays were used: the acetic acid-induced writhing test, hot plate test, hot tail-flick test and formalin test. Three doses were used in the analgesic assays and ED_ (50) valueswere calculated. For the selectivity assay, macrophages were incubated with testcompounds at various concentrations and then stimulated with calcimycin or lipopolysaccharide (LPS). The amounts of 6-keto-prostaglandin F_ (1α (6-keto-PGF_ (1α)) and prostaglandin E_2 (PGE_2) in the supernatant were examined by radioimmunoas-say (RIA) .The selectivity of the test compounds was expressed as the IC_ (50.COX-1) / IC_ (50.COX-2) value.Results: Celecoxib and its 2 derivatives had a significant analgesic effect. ED_ (50) values ​​of celecoxib, PC-406 and PC-407 were 94.2, 67.9, and 63.3 mg / kg , respectively, for the acetic acid-induced writhing test; 104.7, 89.1, and 30.0 mg / kg, respectively, for the hot tail-flic k 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 inhibited COX-1 with IC_ (50) values ​​of 39.8 and 27.5 nmol / L, respectively.PC-406 inhibitedCOX-1 with an IC_ (50) value of more than 1000 nmol / L.The IC_ (50) values for the effect of celecoxib, PC-406 and PC-407 on COX-2 were 4.8, 8.9 and 1.9 nmol / L respectively. The IC 50 COX-2 IC50 for COX- PC-407 were 8.3 and 14.4, respec-tively. For PC-406, the ratio was greater than 112.2. Conlusion: Derivatives of celloxib via substitution with an isopropyl or naphthyl group at the 5 position inthe pyrazole ring still have analgesic effects and the ability to sele ctively inhibitCOX-2. Substitution with a naphthyl group may have more effect on the periph-eral pain pathway, while substitution with an isopropyl group may have more effect on the central pain pathway. This phenomenon arises becouse a partial becausesubitutional with an isopropyl group is more beneficial for COX-2 selectivity thanis substitution with a naphthyl group.