eprintid: 20817
rev_number: 12
eprint_status: archive
userid: 1589
dir: disk0/00/02/08/17
datestamp: 2016-06-09 12:50:37
lastmod: 2024-04-16 09:05:06
status_changed: 2016-06-09 12:50:37
type: article
metadata_visibility: show
creators_name: Fleckenstein, Johannes
creators_name: Sittl, Ruth
creators_name: Averbeck, Beate
creators_name: Lang, Philip M.
creators_name: Irnich, Dominik
creators_name: Carr, Richard W.
title: 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
subjects: ddc-610
divisions: i-61600
abstract: Background: 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).   Methods: 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.   Results: 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.).   Conclusions: Clinical doses of flupirtine reduce the excitability of peripheral myelinated axons.   Trial registration: ClinicalTrials registration is NCT01450865.
date: 2013
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1657510530
own_urn: urn:nbn:de:bsz:16-heidok-208170
language: eng
bibsort: FLECKENSTEACTIVATION2013
full_text_status: public
publication: Journal of Translational Medicine
volume: 11
number: 34
place_of_pub: London
pagerange: 1-13
issn: 1479-5876
citation:   Fleckenstein, Johannes ; Sittl, Ruth ; Averbeck, Beate ; Lang, Philip M. ; Irnich, Dominik ; Carr, Richard W.  (2013) 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.  Journal of Translational Medicine, 11 (34).  pp. 1-13.  ISSN 1479-5876     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/20817/1/12967_2012_Article_1500.pdf