Anti‐inflammatory and antipyretic properties of N‐(α,α,α‐Trifluoro‐m‐tolyl) anthranilic acid (CI‐440; flufenamic acid)

Abstract

Flufenamic acid is more potent than phenylbutazone as an anti-inflammatory agent in guinea pigs (ultraviolet erythema) and rats (granulation on subcutaneous cotton pellets), without evidence of adrenal dependence or cortieoid hormonal effects. Its antipyretic potency in rats approximates that of phenylbutazone. Like phenylbutazone and unlike aminopyrine, it had no antinocicep tive effect in rat tail-pinching experiments. In ordinary concentrations as the sodium salt, it is a tissue irritant in rodents. Supratherapeutic oral doses were well tolerated.Acido flufenamic es plus potente gue phenylbutazona como agente anti-inflammatori in porcos de India (erythema ultraviolette) e rattos (granulation super subcutanee pellets de coton), sin evidentia de dependentia adrenal o de affectos corticoido-hormonal. Su potentia antipyretic in rattos es approximativemente ill0 de phenylbutazona. Como phenylbutazona e per contrast0 con aminopyrina, ill0 habeva nulle eff ecto antinociceptive in experimentos de pinceage de cauda in rattos. In concentrationes ordinari e usate como sal de natrium, ill0 es un irritante de tissu in rodentes. Supratherapeutic doses oral esseva ben tolerate. E HAVE REPORTED that N-( 2,3-~ylyl)anthranilic acid (mefenamic acid) antagonizes the erythema in guinea pigs' skin foIlowing ultra-violet irradiation, and that it partially depresses inflammatory granulation tissue growth, is antipyretic, and is antin0ciceptive.l Such new antipreinflammatory2 compounds provide tests, beyond those provided by agents already known to therapy, of a working hypothesis that the anti-UV-erythema efficacy is closely correlated with and highly predictive of a nonsteroidal kind of antirheumatic efficacy? The compound to be described here, N-( ar,ar,a-trifluoro-m-tolyl ) -anthranilic acid4 (CI-440; flufenamic acid),* was found to be more potent than mefenamic acid or phenylbutazone in antagonizing the UV-erythema. Like phenylbutazone and mefenamic acid, it also partially depresses inflammatory granulation tissue growth and is antipyretic. However, like phenylb~tazone,~ it differs from mefenamic acid in failing to exhibit antinociceptive action in rat tail-pinching experiments. MATERIALS AND METHODSCI-440 i5 a cream-colored, solid carboxylic acid of molecular weight 281.2:From the

Antagonism by fenamates and like‐acting drugs of bronchoconstriction induced by bradykinin or antigen in the guinea‐pig

“…We describe tests of the antagonism by still newer non-steroidal antiinflammatory agents of bradykinin-induced bronchoconstriction. Among these agents meclofenamate showed outstandingly high potency, in keeping with its performance in anti-inflammatory tests (Winder, Wax & Welford, 1965). We also describe fuller tests of some drugs of other types, previously reported to have antibradykinin activity in guinea-pig lungs (Collier, James & Piper, 1965;Simke et al, 1967).…”

Effects of Anti-inflammatory Drugs in Shock Caused by Injection of Living E. coli Cells

“…Shock caused by septicemia is a grave and frequently lethal clinical condition (16). Because of the strikingly beneficial effects of nonsteroidal anti-inflammatory agents in both endotoxin (2-4) and E. toli shock, their use to improve this condition in man may merit consideration.…”

The assay of anti‐pyretic drugs in mice, using intracerebral injection of pyretogenins

“…Yeast induced fever, introduced by Smith & Hambourger (1935) is the most widely used screening test, and has been used for assessing the anti-pyretic activity of non-narcotic analgesic drugs by Boxill, Nash & Wheeler (1958), Domenjoz (1960), Winder, Wax, Scotti, Scherrer, Jones & Short (1962), Adams, Cliffe, Lessel & Nicholson (1963), Rosenthal, Markley & Schubert (1963), Winder, Wax, Serrano, Jones & McPhee (1963 and Winder, Wax & Welford (1965). The test involves injecting a suspension of yeast subcutaneously into rats on the afternoon before the test.…”