Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases

Gen Physiol Biophys. 1994 Aug;13(4):309-28.

Abstract

The actions of psoralens, benzofurans, acridinons and coumarins on the ionic currents in intact myelinated nerve fibres were investigated. All 6 substances blocked the potassium currents in a time-dependent manner, producing so-called K+ transients. Only 5-methoxypsoralen is a largely selective blocker of predominantly the axolemmal potassium channels, which is the characteristic required by our previously proposed working hypothesis for the mechanism of potassium-channel blockers in demyelinating diseases, in particular multiple sclerosis. If the observed K+ transients were to arise by blocking of the potassium channels of the Schwann cell, that is, by the periaxonal accumulation of K+ and a resulting collapse of the electromotive driving force for potassium-ions, according to a modified version of our previous hypothesis the other substances tested could also have a beneficial effect on the impaired impulse conduction in demyelinated axons. In this case a large number of new potential drugs would be available for the symptomatic therapy of MS.

MeSH terms

  • 5-Methoxypsoralen
  • Acridines / pharmacology
  • Animals
  • Benzofurans / pharmacology
  • Biophysical Phenomena
  • Biophysics
  • Coumarins / pharmacology
  • Demyelinating Diseases / drug therapy*
  • Demyelinating Diseases / physiopathology
  • In Vitro Techniques
  • Methoxsalen / analogs & derivatives*
  • Methoxsalen / pharmacology
  • Models, Neurological
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / physiopathology
  • Nerve Fibers, Myelinated / drug effects*
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Fibers, Myelinated / physiology
  • Neural Conduction / drug effects
  • Organophosphorus Compounds / pharmacology
  • Potassium Channel Blockers*
  • Ranvier's Nodes / drug effects
  • Ranvier's Nodes / metabolism
  • Ranvier's Nodes / physiology
  • Umbelliferones / pharmacology
  • Xenopus laevis

Substances

  • 5-acetyl-6-benzyloxy-4,7-dimethoxybenzofuran
  • Acridines
  • Benzofurans
  • Coumarins
  • Organophosphorus Compounds
  • Potassium Channel Blockers
  • Umbelliferones
  • 5-Methoxypsoralen
  • 3-methoxyacridin-9-one
  • 7-dimethylamino-4-methylcoumarin
  • 4-methoxy-N-methylacridin-9-one
  • haloxon
  • Methoxsalen