The blood-brain barrier-permeable catechol-O-methyltransferase inhibitor dinitrocatechol suppresses experimental autoimmune encephalomyelitis

Paul E Polak; Shao Xia Lin; Dale Pelligrino; Douglas L Feinstein

doi:10.1016/j.jneuroim.2014.09.004

The blood-brain barrier-permeable catechol-O-methyltransferase inhibitor dinitrocatechol suppresses experimental autoimmune encephalomyelitis

J Neuroimmunol. 2014 Nov 15;276(1-2):135-41. doi: 10.1016/j.jneuroim.2014.09.004. Epub 2014 Sep 16.

Authors

Paul E Polak¹, Shao Xia Lin¹, Dale Pelligrino¹, Douglas L Feinstein²

Affiliations

¹ Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60612, USA.
² 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.

PMID: 25242632
DOI: 10.1016/j.jneuroim.2014.09.004

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