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Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial

Johannes Fleckenstein1*, Ruth Sittl12, Beate Averbeck2, Philip M Lang1, Dominik Irnich1 and Richard W Carr23

Author Affiliations

1 Department of Anaesthesiology, Multidisciplinary Pain Center, University of Munich, Pettenkoferstr. 8a, Munich 80336, Germany

2 Department of Physiology, Ludwig-Maximilians University, Munich, Germany

3 Department of Anaesthesiology and Intensive Care Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

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Journal of Translational Medicine 2013, 11:34  doi:10.1186/1479-5876-11-34

Published: 8 February 2013



Flupirtine is an analgesic with muscle-relaxing properties that activates Kv7 potassium channels. Kv7 channels are expressed along myelinated and unmyelinated peripheral axons where their activation is expected to reduce axonal excitability and potentially contribute to flupirtine’s clinical profile.

Trial design

To investigate the electrical excitability of peripheral myelinated axons following orally administered flupirtine, in-vitro experiments on isolated peripheral nerve segments were combined with a randomised, double-blind, placebo-controlled, phase I clinical trial (RCT).


Threshold tracking was used to assess the electrical excitability of myelinated axons in isolated segments of human sural nerve in vitro and motoneurones to abductor pollicis brevis (APB) in situ in healthy subjects. In addition, the effect of flupirtine on ectopic action potential generation in myelinated axons was examined using ischemia of the lower arm.


Flupirtine (3-30 μM) shortened the relative refractory period and increased post-conditioned superexcitability in human myelinated axons in vitro. Similarly, in healthy subjects the relative refractory period of motoneurones to APB was reduced 2 hours after oral flupirtine but not following placebo. Whether this effect was due to a direct action of flupirtine on peripheral axons or temperature could not be resolved. Flupirtine (200 mg p.o.) also reduced ectopic axonal activity induced by 10 minutes of lower arm ischemia. In particular, high frequency (ca. 200 Hz) components of EMG were reduced in the post-ischemic period. Finally, visual analogue scale ratings of sensations perceived during the post-ischemic period were reduced following flupirtine (200 mg p.o.).


Clinical doses of flupirtine reduce the excitability of peripheral myelinated axons.

Trial registration

ClinicalTrials registration is NCT01450865.

Kv7 potassium channel; Flupirtine; Human myelinated axon; A fibre; Randomised controlled trial