Effect of the leukotriene B4 receptor antagonist, SC-41930, on experimental allergic encephalomyelitis (EAE) in the guinea pig.
The accepted model for the human demyelinating disease, multiple sclerosis (MS), is experimental allergic encephalomyelitis (EAE). We assessed the ability of SC-41930(7-[3(4-acetyl-3-methoxy-2-propyl-phenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxyl acid), to modulate the symptoms of acute EAE generated in guinea pigs. Animals were pretreated with SC-41930 (20 mg/kg, i.p.) for two days followed by thrice-weekly maintenance. At day 52, a significant number of the SC-41930-treated animals were alive as compared to EAE alone. Control animals had an increase in body weight while EAE animals lost over 20% (p less than 0.5) of their body weight by day 18. SC-41930-treatment significantly reduced, but did not completely inhibit the cachectic response. The results indirectly implicate LTB4 in the pathogenesis of EAE. Agents that modify this model be useful in the treatment of human MS.
Fretland
D J
DJ
Department of Pathology, Searle Research and Development, Skokie, II 60077.
Widomski
D L
DL
Shone
R L
RL
Levin
S
S
Gaginella
T S
TS
D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D006168:Guinea Pigs; D008297:Male; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018102:Receptors, Leukotriene B4; D013116:Spinal Cord / Q000473:pathology
D001578:Benzopyrans; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; C059950:SC 41930