Effect of ETH615, an inhibitor of leukotriene synthesis and IL-8 gene expression, on murine dermatoses.
ETH615 (4-[2-quinolylmethoxy]-N-[3-fluorobenzyl]-phenylaminometh yl-4-benzoic acid) is a potent inhibitor of leukotriene biosynthesis in A23187-stimulated leukocytes, and of IL-8 gene expression in LPS-stimulated PBMC. It shows anti-inflammatory activity in a canine model of dermal inflammation. A topical formulation is present in phase II clinical trials. In the present study the effect of ETH615 on oxazolone-induced acute inflammation and phorbol ester-induced chronic inflammation in the mouse ear was investigated. Betamethasone (0.04 mg/ear) and ETH615 (1-1.5 mg/ear) significantly inhibited both the oedema formation and the PMN infiltration. The cream and ointment formulations of ETH615 developed for clinical studies were equally active. ETH615 is thus an anti-inflammatory agent in these murine models of dermatosis.
Ahnfelt-Rønne
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Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
Aaes
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Skak-Nielsen
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001623:Betamethasone / Q000627:therapeutic use; D003872:Dermatitis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015870:Gene Expression / Q000187:drug effects; D016209:Interleukin-8 / Q000235:genetics; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D051379:Mice; D010081:Oxazolone; D009195:Peroxidase / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D011804:Quinolines; C069967:ETH 615; D010081:Oxazolone; D007975:Leukotriene B4; D001623:Betamethasone; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate