title: The blood-brain barrier-permeable catechol-O-methyltransferase inhibitor dinitrocatechol suppresses experimental autoimmune encephalomyelitis.
abstract: Reduced levels of noradrenaline (NA) in CNS of multiple sclerosis patients could be due to metabolism by catechol-O-methyltransferase (COMT). In mice immunized with myelin oligodendrocyte glycoprotein peptide, the BBB-permeable COMT inhibitor dinitrocatechol (DNC) reduced clinical signs, while entacapone, a non-BBB-permeable inhibitor, had no effect. Spinal cord NA levels were slightly increased by DNC, and there was an inverse correlation between NA levels and average clinical signs. Spinal cord COMT mRNA levels were not increased during EAE, but were found increased in the frontal cortex of MS patients. These results suggest that COMT inhibitors could provide benefit to MS patients.
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Polak
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Shao Xia
authors.initials: SX
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Pelligrino
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Veterans Affairs, Jesse Brown VA Medical Center, Chicago, IL 60612, USA. Electronic address: dlfeins@uic.edu.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Feinstein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000627:therapeutic use*; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D063308:Myelin-Oligodendrocyte Glycoprotein; D009570:Nitriles; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C071192:entacapone; D005620:Freund's Adjuvant; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C057726:OR486
keywords: COMT; Catecholamine; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Noradrenaline