Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases.
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.
Bohuslavizki
K H
KH
Institute of Physiology, University of Kiel, Germany.
Hänsel
W
W
Kneip
A
A
Koppenhöfer
E
E
Niemöller
E
E
Sanmann
K
K
D000078223:5-Methoxypsoralen; D000166:Acridines / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D055592:Biophysical Phenomena; D001703:Biophysics; D003374:Coumarins / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011901:Ranvier's Nodes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014468:Umbelliferones / Q000494:pharmacology; D014982:Xenopus laevis
C092579:5-acetyl-6-benzyloxy-4,7-dimethoxybenzofuran; D000166:Acridines; D001572:Benzofurans; D003374:Coumarins; D009943:Organophosphorus Compounds; D026902:Potassium Channel Blockers; D014468:Umbelliferones; D000078223:5-Methoxypsoralen; C092581:3-methoxyacridin-9-one; C092582:7-dimethylamino-4-methylcoumarin; C092580:4-methoxy-N-methylacridin-9-one; C007902:haloxon; D008730:Methoxsalen