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

Sheng-Nan Wu, Ming Chun Hsu, Yu Kai Liao, Fang Tzu Wu, Yuh Jyh Jong, Yi Ching Lo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number148403
JournalEvidence-based Complementary and Alternative Medicine
Volume2012
DOIs
Publication statusPublished - 2012 Aug 20

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flupirtine
Motor Neurons
Analgesics
linopirdine
GABA Agents
GABA Receptors

All Science Journal Classification (ASJC) codes

  • Complementary and alternative medicine

Cite this

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title = "Evidence for inhibitory effects of flupirtine, a centrally acting analgesic, on delayed rectifier K + currents in motor neuron-like cells",
abstract = "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.",
author = "Sheng-Nan Wu and Hsu, {Ming Chun} and Liao, {Yu Kai} and Wu, {Fang Tzu} and Jong, {Yuh Jyh} and Lo, {Yi Ching}",
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Evidence for inhibitory effects of flupirtine, a centrally acting analgesic, on delayed rectifier K + currents in motor neuron-like cells. / Wu, Sheng-Nan; Hsu, Ming Chun; Liao, Yu Kai; Wu, Fang Tzu; Jong, Yuh Jyh; Lo, Yi Ching.

In: Evidence-based Complementary and Alternative Medicine, Vol. 2012, 148403, 20.08.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for inhibitory effects of flupirtine, a centrally acting analgesic, on delayed rectifier K + currents in motor neuron-like cells

AU - Wu, Sheng-Nan

AU - Hsu, Ming Chun

AU - Liao, Yu Kai

AU - Wu, Fang Tzu

AU - Jong, Yuh Jyh

AU - Lo, Yi Ching

PY - 2012/8/20

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AB - 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.

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