benzofurans and haloxon

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.

Topics: 5-Methoxypsoralen; Acridines; Animals; Benzofurans; Biophysical Phenomena; Biophysics; Coumarins; Demyelinating Diseases; In Vitro Techniques; Methoxsalen; Models, Neurological; Multiple Sclerosis; Nerve Fibers, Myelinated; Neural Conduction; Organophosphorus Compounds; Potassium Channel Blockers; Ranvier's Nodes; Umbelliferones; Xenopus laevis