[Neuronal potassium channel opening with flupirtine].
The spectrum of action of flupirtine includes analgesic, muscle-relaxant and neuroprotective properties. The substance's mechanism of action has yet to be fully explained. Over the past few years, however, evidence has accumulated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effect on the NMDA receptor, all of the findings pointed to an indirect influence on the NMDA receptor in the sense of a functional NMDA antagonism. It was thus postulated that a site of action "up- or downstream" of the NMDA receptor is influenced. Such a site of action proved to be the G-protein-activated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilization of the resting membrane potential of neuronal cells and thus causes an indirect inhibition of the NMDA receptor. At therapeutically relevant concentrations, flupirtine is a neuronal potassium channel opener. This mechanism may explain the spectrum of action of flupirtine. Selective neuronal potassium channel opening (SNEPCO) thus proves to be a new principle of action, making flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimental basis for this working hypothesis and the resulting model concepts are presented from the perspective of a four-stage approach.
Kornhuber
J
J
Psychiatrische Klinik, Universität Göttingen. jkornhu@popper.gwdg.de
Maler
M
M
Wiltfang
J
J
Bleich
S
S
Degner
D
D
Rüther
E
E
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*
D000631:Aminopyridines; D018696:Neuroprotective Agents; D015221:Potassium Channels; C034161:flupirtine
Neuronale Kaliumkanalöffnung durch Flupirtin.