Potassium channel blocker, 4-aminopyridine-3-methanol, restores axonal conduction in spinal cord of an animal model of multiple sclerosis.

Abstract

Multiple sclerosis (MS) is a severely debilitating neurodegenerative diseases marked by progressive demyelination and axonal degeneration in the CNS. Although inflammation is the major pathology of MS, the mechanism by which it occurs is not completely clear. The primary symptoms of MS are movement difficulties caused by conduction block resulting from the demyelination of axons. The possible mechanism of functional loss is believed to be the exposure of potassium channels and increase of outward current leading to conduction failure. 4-Aminopyridine (4-AP), a well-known potassium channel blocker, has been shown to enhance conduction in injured and demyelinated axons. However, 4-AP has a narrow therapeutic range in clinical application. Recently, we developed a new fast potassium channel blocker, 4-aminopyridine-3-methanol (4-AP-3-MeOH). This novel 4-AP derivative is capable of restoring impulse conduction in ex vivo injured spinal cord without compromising the ability of axons to follow multiple stimuli. In the current study, we investigated whether 4-AP-3-MeOH can enhance impulse conduction in an animal model of MS. Our results showed that 4-AP-3-MeOH can significantly increase axonal conduction in ex vivo experimental autoimmune encephalomyelitis mouse spinal cord.

• Authors: Gary Leung, Wenjing Sun, Sarah Brookes, Daniel Smith, Riyi Shi
• Journal: Experimental neurology (Exp Neurol) Vol. 227 Issue 1 Pg. 232-5 (Jan 2011) ISSN: 1090-2430 [Electronic] United States
• PMID: 21093437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• 4-aminopyridine-3-methanol
• Aminopyridines
• Glycoproteins
• Myelin-Oligodendrocyte Glycoprotein
• Neurofilament Proteins
• Peptide Fragments
• Potassium Channel Blockers
• myelin oligodendrocyte glycoprotein (35-55)
• neurofilament protein H

Topics

• Action Potentials (drug effects)
• Aminopyridines (pharmacology, therapeutic use)
• Animals
• Axons (drug effects, physiology)
• Disease Models, Animal
• Glycoproteins (adverse effects)
• Mice
• Mice, Inbred C57BL
• Multiple Sclerosis (chemically induced, drug therapy, pathology)
• Myelin Sheath (metabolism)
• Myelin-Oligodendrocyte Glycoprotein
• Neural Conduction (drug effects)
• Neurofilament Proteins (metabolism)
• Peptide Fragments (adverse effects)
• Potassium Channel Blockers (pharmacology, therapeutic use)
• Reaction Time (drug effects)
• Spinal Cord (drug effects, physiopathology)