H. Niki et al., EFFECTS OF JTE-522, A SPECIFIC INHIBITOR OF CYCLOOXYGENASE-2, ON THE RECURRENCE OF ALLERGIC INFLAMMATION IN RATS, European journal of pharmacology, 344(2-3), 1998, pp. 261-267
JTE-522, l-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, is a selec
tive inhibitor of cyclooxygenase-2 at the enzyme level (IC50 is 6.4 x
10(-7) M for sheep cyclooxygenase-2, but it does not inhibit sheep cyc
looxygenase-1 at concentrations up to 10(-4) M). In rat peritoneal mac
rophages in culture, it markedly inhibited cyclooxygenase-2-dependent
prostaglandin E-2 production and weakly inhibited cyclooxygenase-1-dep
endent prostaglandin E-2 production, as did the selective cyclooxygena
se-2 inhibitor NS-398 cyclohexyloxy-4-nitrophenyl)]-methanesulfonamide
). In addition, the anti-inflammatory activity of JTE-522 was evaluate
d, using a model of recurrent air pouch-type allergic inflammation in
rats. JTE-522, injected into the pouch just after a second antigen cha
llenge, suppressed the accumulation of pouch fluid, the infiltration o
f leukocytes and the prostaglandin E-2 content in the pouch fluid: as
did NS-398 and indomethacin. These findings indicated that JTE-522 is
a selective cyclooxygenase-2 inhibitor in cell culture systems and tha
t the suppression by JTE-522 of the recurrence of allergic inflammatio
n is due to the inhibition of cyclooxygenase-2. (C) 1998 Elsevier Scie
nce B.V.