Evidence for Inhibitory Effects of Flupirtine, a Centrally Acting Analgesic, on Delayed Rectifier K+ Currents in Motor Neuron-Like Cells

Abstract EN

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 (IK(DR)) with a concomitant raise in current inactivation in NSC-34 neuronal cells.

The dissociation constant for Flu-mediated increase of IK(DR) inactivation rate was about 9.8 μM.

Neither linopirdine (10 μM), NMDA (30 μM), nor gabazine (10 μM) reversed Flu-induced changes in IK(DR) inactivation.

Addition of Flu shifted the inactivation curve of IK(DR) to a hyperpolarized potential.

Cumulative inactivation for IK(DR) was elevated in the presence of this compound.

Flu increased the amplitude of M-type K+ current (IK(M)) and produced a leftward shift in the activation curve of IK(M).

In another neuronal cells (NG108-15), Flu reduced IK(DR) amplitude and enhanced the inactivation rate of IK(DR).

The results suggest that Flu acts as an open-channel blocker of delayed-rectifier K+ channels in motor neurons.

Flu-induced block of IK(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.