Evidence for inhibitory effects of flupirtine, a centrally acting analgesic, on delayed rectifier K ⁺ currents in motor neuron-like cells

Flupirtine (Flu), a triaminopyridine derivative, is a centrally acting, non-opiate analgesic agent. In this study, effects of Flu on K ⁺ currents were explored in two types of motor neuron-like cells. Cell exposure to Flu decreased the amplitude of delayed rectifier K ⁺ current (I K (DR)) with a concomitant raise in current inactivation in NSC-34 neuronal cells. The dissociation constant for Flu-mediated increase of I K (DR) inactivation rate was about 9.8M. Neither linopirdine (10M), NMDA (30M), nor gabazine (10M) reversed Flu-induced changes in I K (DR) inactivation. Addition of Flu shifted the inactivation curve of I K (DR) to a hyperpolarized potential. Cumulative inactivation for I K (DR) was elevated in the presence of this compound. Flu increased the amplitude of M-type K ⁺ current (I K (M)) and produced a leftward shift in the activation curve of I K (M). In another neuronal cells (NG108-15), Flu reduced I K (DR) amplitude and enhanced the inactivation rate of I K (DR). The results suggest that Flu acts as an open-channel blocker of delayed-rectifier K ⁺ channels in motor neurons. Flu-induced block of I K (DR) is unlinked to binding to NMDA or GABA receptors and the effects of this agent on K ⁺ channels are not limited to its action on M-type K ⁺ channels.