Suppression of acute experimental allergic encephalomyelitis in Lewis rats with a mycophenolic acid derivative.
Oral administration of ethyl O-[N-(p-carboxyphenyl-carbamoyl]-mycophenolate (CAM), a derivative of mycophenolic acid (MPA) and an inosine monophosphate dehydrogenase inhibitor, dose-dependently suppressed acute experimental allergic encephalomyelitis in Lewis rats without exerting any serious adverse effects. A daily dose of 50 mg/kg of CAM almost completely abolished both the clinical disease and the inflammation in the CNS. In the CAM-treated rats, a weight loss and fluctuations of peripheral lymphocyte subsets were minimized. The CAM treatment was effective when started at the time of sensitization but ineffective when deferred till day 10. Furthermore, CAM reduced the percentage of CD4+CD45RC- cells in the peripheral blood. The only detectable adverse effect was moderate anemia but it was rapidly improved after withdrawal of the drug. This drug could be a useful adjunct for the long-term immunosuppressive therapy for inflammatory diseases of the CNS.
Mizobuchi
M
M
Department of Neurology, Nakamura Memorial Hospital, Sapporo, Japan.
Iwasaki
Y
Y
Sako
K
K
Kaneko
Y
Y
D000284:Administration, Oral; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; C031864:ethyl O-(N-(4-carboxyphenyl)carbamoyl)mycophenolate; D009173:Mycophenolic Acid