AMPA type glutamate receptors have major roles in excitatory fast synaptic transmission in CNS and the excessive activation of the receptors is implicated in the pathogenesis of various neurodegenerative diseases. Recent studies have indicated that antagonism at AMPA receptors affects the disease process of experimental autoimmune encepharomylelitis (EAE) (Nature Med. (2000) 6, 62; Ohgoh et al., SFN 2001 abstract). Thus orally active antagonists of the AMPA type glutamate receptors might be useful for the treatment of multiple sclerosis. ER-099487 is a highly selective AMPA type glutamate receptor antagonist as shown by in vitro and in vivo assays (Ueno et al. SFN 2001 abstract). To examine the effect of ER-099487 in EAE, disease ameliorative effect of ER-099487 was evaluated in an acute Lewis rat EAE model. ER-099487 was administered orally between 7 and 16 days post immunization (dpi). This treatment dose-dependently reduced disease severity and delayed the onset of the disease. The treatment of animals ...