A study of the novel anti-inflammatory agent florifenine topical anti-inflammatory activity and influence on arachidonic acid metabolism and neutrophil functions.
We have evaluated the effects of the novel anti-inflammatory agent florifenine, 2-(1-Pyrrolidinyl)ethyl N-[7-(trifluoromethyl)-4-quinolyl]anthranilate, on topical inflammation in mice, free radical-mediated reactions, arachidonic acid metabolism and some neutrophil functions. Topical administration of florifenine produced dose-related anti-inflammatory activity in 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and with a lower potency, in the response induced by arachidonic acid (AA). Florifenine also inhibited neutrophil migration and PGE2 content in the inflammed ears. In human whole blood, florifenine was a potent and selective inhibitor of TXB2 generation. This anti-inflammatory agent did not exert antioxidant effects but inhibited elastase release in human neutrophils without affecting superoxide anion generation. Florifenine administration to mice dose-dependently inhibited leukocyte migration and PGE2 levels in the air pouch inflammation induced by zymosan. These results demonstrate the topical anti-inflammatory activity of florifenine and provide a basis for understanding the mechanisms involved in the inhibitory effects of this agent on inflammatory responses.
Bustos
G
G
Departamento de Farmacología, Universidad de Valencia, Facultad de Farmacia, Spain.
Ferrándiz
M L
ML
Sanz
M J
MJ
Payá
M
M
Alcaraz
M J
MJ
D000287:Administration, Topical; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004487:Edema / Q000188:drug therapy; D015777:Eicosanoids / Q000096:biosynthesis; D016166:Free Radical Scavengers; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D019272:Leukocyte Elastase; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000634:Aminoquinolines; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015777:Eicosanoids; D016166:Free Radical Scavengers; D011759:Pyrrolidines; D013481:Superoxides; D016718:Arachidonic Acid; D017665:Hydroxyl Radical; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate; C094622:florifenine