Opening of neuronal K+ channels by flupirtine

The spectrum of action of flupirtine includes analgesic, muscle-relaxant an d neuroprotective properties. The substance's mechanism of action has yet t o be fully explained. Over the past few years, however, evidence has accumu lated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effe ct an the NMDA receptor, all of the findings pointed to an indirect influen ce on the NMDA receptor in the sense of a functional NMDA antagonism. It wa s thus postulated that a site of action "up- or downstream" of the NMDA rec eptor is influenced. Such a site of action proved to be the G-protein-activ ated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilisation of the resting membrane potential of neuronal cells and thu s causes an indirect inhibition of the NMDA receptor. At therapeutically re levant concentrations, flupirtine is a neuronal potassium channel opener. T his mechanism may explain the spectrum of action of flupirtine. Selective n euronal potassium channel opening (SNEPCO) thus proves to be a new principl e of action, malting flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimenta l basis for this working hypothesis and the resulting model concepts are pr esented from the perspective of a four-stage approach.