Damage to axons and neurons in multiple sclerosis (MS) is increasingly recognized as the major neuropathological correlate of disease progression. 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). Antagonists of the AMPA glutamate receptor, effective neuroprotectants, ameliorate EAE independently of immunosuppression [Nat. Med. (2000) 6:62-66; 6:67-70] suggesting either a neuro- and/or oligodendroglial-protective mechanism of action. Here, we describe the effect of a potent, water-soluble AMPA receptor antagonist, E2007 [profiled in Tokuhara et al and Hashizume et al SFN, 2002], on the course of EAE in Lewis rats [see also Yamauchi et al SFN, 2002]. E2007 (5, 10 and 20 mg/kg; p.o. 7-16 dpi) dose dependently improved neurological status without effecting CNS inflammation or peripheral MBP antibody production. Furthermore, t...