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.
Keywords:
COMT; Catecholamine; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Noradrenaline.
Published by Elsevier B.V.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aged
-
Aged, 80 and over
-
Animals
-
Blood-Brain Barrier / drug effects
-
Blood-Brain Barrier / physiology
-
Catechol O-Methyltransferase / genetics
-
Catechol O-Methyltransferase / metabolism
-
Catechol O-Methyltransferase Inhibitors / therapeutic use*
-
Catechols / pharmacology
-
Catechols / therapeutic use*
-
Disease Models, Animal
-
Encephalomyelitis, Autoimmune, Experimental / chemically induced
-
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
-
Encephalomyelitis, Autoimmune, Experimental / pathology
-
Female
-
Freund's Adjuvant / toxicity
-
Humans
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Middle Aged
-
Multiple Sclerosis / complications
-
Multiple Sclerosis / pathology
-
Myelin-Oligodendrocyte Glycoprotein / toxicity
-
Nitriles / pharmacology
-
Nitriles / therapeutic use
-
Peptide Fragments / toxicity
-
Spinal Cord / drug effects
-
Spinal Cord / metabolism
-
Spinal Cord / pathology
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / metabolism
-
Time Factors
Substances
-
Catechol O-Methyltransferase Inhibitors
-
Catechols
-
Myelin-Oligodendrocyte Glycoprotein
-
Nitriles
-
Peptide Fragments
-
myelin oligodendrocyte glycoprotein (35-55)
-
entacapone
-
Freund's Adjuvant
-
COMT protein, human
-
Catechol O-Methyltransferase
-
OR486