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Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224‐015, an inhibitor of the interleukin‐1β converting enzyme
Author(s) -
Elford P.R.,
Heng R.,
Révész L.,
MacKenzie A.R.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14974.x
Subject(s) - ed50 , pharmacology , oral administration , enzyme inhibitor , analgesic , glucocorticoid , inflammation , chemistry , adrenalectomy , medicine , enzyme , endocrinology , biochemistry , in vitro
1 The aim of this study was to determine whether a synthetic inhibitor of the interleukin‐1β converting enzyme (ICE) displays oral activity in models of inflammation. 2 To this end, the ICE inhibitor, SDZ 224‐015, was examined in rat paw oedema, pyrexia and nociception tests. 3 SDZ 224‐015 (0.3–300 μg kg −1 ) potently reduced carrageenin‐induced paw oedema, with an oral ED 50 of approximately 25 μg kg −1 . This effect was independent of endogenous glucocorticoid, as shown by retention of activity upon adrenalectomy. 4 Pyrexia induced by lipopolysaccharide (0.1 mg kg −1 s.c.) or by interleukin‐1β (100 ng i.v.) was also reduced, over a similar dose‐range to oedema (oral ED 50 S 11 μg kg −1 and 4 μg kg −1 respectively). 5 SDZ 224‐015 (0.2–5 mg kg −1 , p.o.) displayed analgesic activity in the Randall‐Selitto yeast‐inflamed paw pressure test, significant at a dose of 1 mg kg −1 , p.o. 6 Thus, SDZ 224‐015 has potent oral activity in several acute models for inflammation, suggesting that ICE inhibitors may constitute a novel type of anti‐inflammatory agent.