A Study of the Immunosuppressive Properties of Sch 24937

Abstract

Sch 24937 (6-bromo-5-chloro-2-1[(methylsulfonyl) acetyl] 3-(2-pyridyl indole) was previously shown to be an immunosuppressant with potent inhibitory effects on B lymphocyte mediated immune responses. The present investigation was primarily designed to compare the immunopharmacological profile of Sch 24937 with that of cyclosporin A (CSA) a well-known immunosuppressive drug that has selective effects on T-lymphocyte-mediated immune responses. The results show that while the immunosuppressive activity of CSA in vitro is superior to that of Sch 24937, in general the latter agent is a more potent inhibitor of immune responses in vivo. The activity of Sch 24937 in rat models of adjuvant arthritis and experimental allergic encephalomyelitis is also described. While Sch 24937 exhibits the type of immunopharmacological profile that is likely to yield a good therapeutic effect in the treatment of immune-mediated chronic inflammatory diseases, hepatotoxicity associated with the compound precludes its development for the treatment of non-life threatening human autoimmune conditions.