title: Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases.
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.
authors.affiliation: Institute of Physiology, University of Kiel, Germany.
authors.forename: K H
authors.initials: KH
authors.lastname: Bohuslavizki
authors.forename: W
authors.initials: W
authors.lastname: Hänsel
authors.forename: A
authors.initials: A
authors.lastname: Kneip
authors.forename: E
authors.initials: E
authors.lastname: Koppenhöfer
authors.forename: E
authors.initials: E
authors.lastname: Niemöller
authors.forename: K
authors.initials: K
authors.lastname: Sanmann
mesh_terms: 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
chemical_list: 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