Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abramson SB, Leszczynska-Piziak J, Clancy RM, Philips M, NWeissmann G (1994) Inhibition of neutrophil function by aspirin-like drugs (NSAIDS): requirement for assembly of heterotrimeric G proteins in bilayer phospholipid. Biochem Pharmacol 47:563–572
Bergmeyer HU, Bernt E (1974) Lactate dehydrogenase: UV assay with pyruvate and NADH: In: Bergmeyer HU (ed) Methods of enzymatic analyssis. Academic Press, New York, pp 574–577
Blackwell GJ, Flower RJ (1983) Inhibition of phospholipase. Br Med Bull 39:260–264
Carlson RP, O'Neill-Davis L, Chang J, Lewis AJ (1985) Modulation of mouse ear edema by cyclooxygenase and lipoxygenase inhibitors and other pharmacologic agents. Agents Action 17:197–204
De Young LM, Kheifets JB, Ballaron SJ, Young JM (1989) Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differntially modulated by pharmacologic agents. Agents Actions 26:335–341
Edwards JCW, Sedgwick AD, Willoughhy DA (1981) The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. J Pathol 134:147–156
Emerit I, Arutyunyan R, Sarkisian T, Mejlumian H, Torosian E, Panossian AG (1993) Oxyradical-mediated chromosome damage in patients with familial Mediterranean fever. Free Rad Biol Med 15:265–271
Foguet R, Ortiz JA, Forné E, Sacristán A (1982) Procedimiento de obtención de nuevos derivados del ácido 2-aminobenzoico. Patent 512605
Halliwell B (1990) How to characterize a biological antioxidant. Free Rad Res Commun 9:1–32
Higgs GA, Vane JR (1983) Inhibition of cyclo-oxygenase and lipoxygenase. Br Med Bull 39:265–270
Inoue H, Mori T, Shibata S, Koshihara Y (1989) Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema. Br J Pharmacol 96:204–210
Kaplan HB, Edelson Hs, Korchak HM, Given WP, Abramson S, Weissmann G (1984) Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo. Biochem Pharmacol 33:371–378
Llerena A, Cobaleda J, Benítez J, Márquez M, Casafont J, Torres J, Vergés J, Ortiz JA (1991) Estudio en fase I de florifenina administrada tópicamente a dosis multiples crecientes durante 14 días. IV Reunión conjunta de las Sociedades Portuguesa y Española de Farmacología Lisboa, Portugal
Mansuy D, Sassi A, Dansette PM, Plat M (1986) A new potent inhibitor of lipid peroxidation in vitro and in vivo, the hepatoprotective drug anisyldithiolthione. Biochem Biophys Res Commun 135:1015–1021
Moore AR, Iwamura H, Larbre JP, Scott DL, Willoughby DA (1993) Cartilage degradation by polymorphonuclear leucocytes: in vitro assessment of the pathogenic mechanisms. Ann Rheum Dis 52:27–31
Moroney MA, Alcaraz MJ, Forder RA, Carey F, Hoult JRS (1988) Selectivity of neutrophil 5-lipoxygenase and cyclo-oxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. J Pharm Pharmacol 40:787–792
Naccache PH, McColl SR, Caon Ac, Borgeat P (1989) Arachidonic acid-induced mobilization of calcium in human neutrophils: evidence for a multicomponent mechanism of action. Br J Pharmacol 97:461–468
Neal TM, Vissers MCM, Winterbourn CC (1987) Inhibition by nonsteroidal anti-inflammatory drugs of superoxide production and granule enzyme release by polymorphonuclear leukocytes stimulated with immune complexes or formyl-methionyl-leucyl-phenylalanine. Biochem Pharmacol 36:2511–2517
Payá M, Halliwell B, Hoult JRS (1992) Interactions of a series of coumarins with reactive oxygen species: scavenging of superoxide, hypochlorous acid and hydroxyl radicals. Biochem Pharmacol 44:205–214
Payá M, Ferrándiz ML, Miralles F, Montesinos C, Ubeda A, Alcaraz MJ (1993) Effects of coumarin derivatives on superoxide anion generation. Arzneim Forsch 43:655–658
Slater TF, Sawyer BC (1971) The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reaction in rat liver fractions in vitro. Biochem J 123:805–814
Smith RJ, Sam LM, Justen JM, Leach KL, Epps DE (1987) Human polymorphonuclear neutrophil activation with arachidonic acid. Br J Pharmacol 91:641–649
Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T (1983) Assay method for mycloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 132:345–352
Twomey BM, Dale MM (1992) Cyclooxygenase-independent effects of non-steroidal anti-inflammatory drugs on the neutrophil respiratory burst. Biochem Pharmacol 43:413–418
Ubeda A, Montesinos C, Payá M, Alcaraz MJ (1993) Iron reducing and free radical scavenging properties of apomorphine and some related benzylisoquinolines. Free Rad Biol Med 15:159–167
Walsh C, Dechatelet LR, Chilton FH, Wykle RL, Waite M (1983) Mechanism of arachidonic acid release in human polymorphonuclear leukocytes. Biochim Biophys Acta 750:32–40
Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376
Williams TJ (1983) Interactions between prostaglandsin, leukotrienes and other mediators of inflammation. Br Med Bull 39:239–242
Winterbourn CC (1993) Superoxide as an intracellular radical sink. Free Rad Biol Med 14:85–90
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bustos, G., Ferrándiz, M.L., Sanz, M.J. et al. A study of the novel anti-inflammatory agent florifenine topical anti-inflammatory activity and influence on arachidonic acid metabolism and neutrophil functions. Naunyn-Schmiedeberg's Arch Pharmacol 351, 298–304 (1995). https://doi.org/10.1007/BF00233250
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00233250