Anti-arthritic properties of ICI 55897 (Clozic) (Abstract)

Abstract

ICI 55897 has a novel spectrum of properties in experimental models of inflammation when compared with conventional non-steroidal antiinflammatory drugs (NSAIDS). A chronic, persistent form of rat adjuvant arthritis is inhibited by ICI 55897, but otherwise the molecule possesses minimal activity in standard anti-inflammatory and analgesic tests. For example, ICI 55897 has little or no activity in the acute, carrageenin oedema test in the rat, at doses and serum levels which are many times higher than those necessary to inhibit the chronic model of adjuvant arthritis. In further contrast to the NSAIDS, ICI 55897 produces no gastrointestinal irritation in laboratory animals. This different spectrum of activity of ICI 55897, in comparison with the NSAIDS, may be explained by the very weak inhibitory activity of ICI 55897 against prostaglandin synthetase, i.e., the enzyme system which is the target of the NSAIDS. ICI 55897 inhibits a chronic form of arthritis in the rat, but not by an inhibition of the overlying acute symptoms of the inflammatory process. Clinical results, to date, have substantiated this view. ICI 55897 has demonstrated an effect against human rheumatoid arthritis which is similar to that produced by the disease modifying agents, gold and pencillamine, rather than the symptomatic effect produced by the NSAIDS.