Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment.

Article Details

Citation

Judge SI, Bever CT Jr

Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment.

Pharmacol Ther. 2006 Jul;111(1):224-59. Epub 2006 Feb 9.

PubMed ID
16472864 [ View in PubMed
]
Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by demyelination, with a relative sparing of axons. In MS patients, many neurologic signs and symptoms have been attributed to the underlying conduction deficits. The idea that neurologic function might be improved if conduction could be restored in CNS demyelinated axons led to the testing of potassium (K(+)) channel blockers as a symptomatic treatment. To date, only 2 broad-spectrum K(+) channel blockers, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP), have been tested in MS patients. Although both 4-AP and 3,4-DAP produce clear neurologic benefits, their use has been limited by toxicity. Here we review the current status of basic science and clinical research related to the therapeutic targeting of voltage-gated K(+) channels (K(v)) in MS. By bringing together 3 distinct but interrelated disciplines, we aim to provide perspective on a vast body of work highlighting the lengthy and ongoing process entailed in translating fundamental K(v) channel knowledge into new clinical treatments for patients with MS and other demyelinating diseases. Covered are (1) K(v) channel nomenclature, structure, function, and pharmacology; (2) classic and current experimental morphology and neurophysiology studies of demyelination and conduction deficits; and (3) a comprehensive overview of clinical trials utilizing 4-AP and 3,4-DAP in MS patients.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
DalfampridinePotassium voltage-gated channel subfamily A member 1ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 10ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 2ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 3ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 4ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 5ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 6ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily A member 7ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily B member 1ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily B member 2ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily C member 1ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily C member 2ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily C member 3ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily D member 1ProteinHumans
Yes
Antagonist
Details
DalfampridinePotassium voltage-gated channel subfamily D member 3ProteinHumans
Yes
Antagonist
Details