Effects of silperisone on the excitation process in Ranvier nodes.
The effect of silperisone on single intact Ranvier nodes of the toad Xenopus was investigated by adding it to the bathing medium. At 100 micromol/l the following fully reversible effects were observed: 1. The spike amplitude decreased in a frequency-dependent manner. 2. Both the sodium activation and the inactivation curves as well as the potential dependence of taum were slightly shifted in the negative direction, while tauh did not change. 3. The sodium permeability constant PNa decreased by 50%. 4. The potassium currents acquired a phasic time course previously described for certain psoralens. They reached a relative maximum and then approached a lower steady state value, kappa(infinity) with a time constant of about 5 ms. Concentration-related responses of PNa, PK and of k(infinity), yielded: 5. The apparent dissociation constant of block of PNa was 110 micromol/l. 6. PK proved not to be changed by silperisone in the concentration range tested, while the variable kappa(infinity) yielded a relation similar to that of PNa except that the apparent dissociation constant was 24 micromol/l. The phasic course of the potassium currents in the presence of silperisone may be due to an open channel blockade. In view of the similarities between the actions of silperisone and 5-methoxypsoralen, it is entirely conceivable that silperisone has potential for an antispastic drug, e.g., in demyelinating diseases like multiple sclerosis.
Düring
T
T
Institute of Physiology, University of Kiel, Germany.
Koppenhöfer
E
E
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002138:Calibration; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010539:Permeability; D010880:Piperidines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011901:Ranvier's Nodes / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014982:Xenopus laevis
D001555:Benzene Derivatives; D010276:Parasympatholytics; D010880:Piperidines; D026902:Potassium Channel Blockers; D015222:Sodium Channels; D012964:Sodium; C445662:silperisone