Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Currently, no adequate therapy is available for MS, despite immunomodulatory measures. The pathological and clinical features of MS can be reproduced in rodent models, collectively termed experimental autoimmune encephalomyelitis (EAE). Previously, we and others [Nat. Med. (2000) 6:62-66; 6:67-70] demonstrated that AMPA receptor antagonists were effective in ameliorating EAE [see also Hanada et al and Ohgoh et al SFN 2001 abstracts]. These effects were independent of immunomodulatory action suggesting either a neuro- and/or oligodendroglial-protective mechanism of action. Here we describe the effect of a potent, water soluble AMPA receptor antagonist, ER-167288-01, on the course of EAE. Two acute EAE models in Lewis rats were used: (1) active induction with myelin basic protein (MBP) in FCA with M. tuberculosis; (2) adoptive transfer of MBP-sensitised spleen cells. ER-167288-01 (30 or 50 mg/kg; i.p. twice daily ...