Effects of SA6541, a leukotriene A4 hydrolase inhibitor, and indomethacin on carrageenan-induced murine dermatitis.
We investigated the effects of S-(4-dimethylaminobenzyl)-N-[(2S)-3-mercapto-2-methylpropionyl]-L- cysteine (SA6541), a potent leukotriene A4 hydrolase inhibitor. on early phase of carrageenan-induced dermatitis model. Carrageenan injection induced edema and neutrophil influx in the mouse ear. SA6541 inhibited edema formation and neutrophil influx. SA6541 also inhibited leukotriene B4 production but not prostaglandin E2 production in the mouse ear. On the other hand, indomethacin inhibited edema formation but not neutrophil influx. Indomethacin also inhibited prostaglandin E2 production but not leukotriene B4 production. Combination therapy with SA6541 and indomethacin strongly inhibited edema formation in comparison with treatment with either agent alone. These results suggest that leukotriene B4 may be important in the pathogenesis of dermatitis.
Tsuji
F
F
Discovery Research Division, Santen Pharmaceutical, Osaka, Japan.
Miyake
Y
Y
Enomoto
H
H
Horiuchi
M
M
Mita
S
S
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000378:metabolism / Q000517:prevention & control*; D004487:Edema / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D007213:Indomethacin / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000814:Aniline Compounds; D004791:Enzyme Inhibitors; C110878:SA 6541; D007975:Leukotriene B4; D002351:Carrageenan; D004851:Epoxide Hydrolases; D003545:Cysteine; C043134:leukotriene A4 hydrolase; D007213:Indomethacin