Neuronale Kaliumkanalöffnung durch Flupirtin
| Autor: | Jens Wiltfang, Stefan Bleich, M. Maler, Johannes Kornhuber, Detlef Degner, E. Rüther |
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| Rok vydání: | 1999 |
| Předmět: |
040301 veterinary sciences
Chemistry 04 agricultural and veterinary sciences Neuroprotection Potassium channel 0403 veterinary science 03 medical and health sciences Psychiatry and Mental health Glutamatergic 0302 clinical medicine nervous system Neurology Mechanism of action medicine NMDA receptor Potassium channel opener Neurology (clinical) G protein-coupled inwardly-rectifying potassium channel medicine.symptom Flupirtine Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Fortschritte der Neurologie · Psychiatrie. 67:466-475 |
| ISSN: | 1439-3522 0720-4299 |
| DOI: | 10.1055/s-2007-994997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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