ACYLPHENOTIAZINE ANTIINFLAMMATORY AGENTS WITH STEROID-LIKE ACTIVITY. I. 2-CHLORO-10-(-DIMETHYL-AMINOPROPIONYL)-PHENOTHIAZINE-5-OXIDE HYDROCHLORIDE

¹ Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania

SK& F 17910-A, (2-chloro-1O-(-dimethylaminopropionyl)-pheno-thiazine-5-oxide hydrochloride), has antiinflammatory activity qualitatively and quantitatively similar to that produced by hydrocortisone. Oral antiinflammatory activity of SK& F 17910-A was 15 to 03 times that of hydrocortisone in intact animals, using the pleural fluid, rat paw edema, carrageenan abscess and granuloma tests. SK& F 17910-A exhibited some thymolytic activity but did not cause adrenal atrophy or hyperplasia. In adrenolectomized (ADX) animals, SK& F 17910-A had a quantitatively similar antiinflammatory activity, clearly demonstrating that this activity was not the result of adrenal stimulation. Although SK& F 17910-A shares the antiiiiflammatory activity of hydrocortisone, it differs from hydrocortisone in having no effect upon glycogen deposition. But again, like hydrocortisone, SK& F 17910-A was inactive in the ultraviolet (UV) erythema test, a procedure which actively selects the known nonsteroidal antiinflammatory agents. In the water-unloading test in ADX rats, SK& F 17910-A and the glucocorticoids were unique in their ability to repair the defects in the excretion of a water load. Since other nonsteroidal antiinflammatory compounds were inactive in this procedure, it is concluded that SK& F 17910-A is a unique nonsteroidal antiinflammatory agent having some of the properties of the glucocorticoids.