Topical antiseptics for the treatment of sore throat block voltage-gated neuronal sodium channels in a local anaesthetic-like manner
- 300 Downloads
Lozenges for the treatment of sore throat provide relief of discomfort in cases of oral inflammation. This effect has not been fully explained so far. Here, we have examined the proposition that key components of pharmaceutical preparations for the treatment of sore throat which are routinely regarded antiseptics might have sodium channel-blocking, i.e. local anaesthetic-like effects. We investigated the effects of hexylresorcinol, amylmetacresol and dichloro-benzylalcohol on voltage-operated neuronal (NaV1.2) sodium channels heterologously expressed in HEK 293 cells in vitro. Hexylresorcinol, amylmetacresol and dichloro-benzylalcohol reversibly blocked depolarisation-induced whole-cell sodium inward currents. The half-maximum blocking concentrations (EC50) at −150 mV were 23.1, 53.6 and 661.6 µM, respectively. Block induced by hexylresorcinol and amylmetacresol was increased at depolarised potentials and use-dependent during trains of depolarisations applied at high frequency (100 Hz) indicating that both drugs bind more tightly to inactivated conformations of the channel. Estimates for the inactivated state affinity were 1.88 and 35 µM for hexylresorcinol and amylmetacresol, respectively. Hexylresorcinol and amylmetacresol are 10–20 fold more potent than the local anaesthetic lidocaine in blocking sodium inward current. Both drugs show an increased effect at depolarised membrane potentials or in conditions of high-frequency discharges.
KeywordsSodium channels Voltage-operated Local anaesthetic Hexylresorcinol Amylmetacresol Dichloro-benzylalcohol
We are indebted to Prof. Frank Lehmann-Horn, Ulm, Germany, for providing us with transfected cells, to Jobst Kilian and Andreas Niesel, Dept. of Neurology, Hannover, Germany, for technical support and to Irene Wirszins, Dept. of Anaesthesiology, Hannover, Germany, for taking care of the cell culture.
Statement of conflict of interest
This work was supported by an unrestricted grant from Reckitt Benckiser to Martin Leuwer.
- Berry P (2008) Rapid relief of acute sore throat with Strepsils lozenges: a single-blind comparative study. Royal Society of Medicine Press, London. ISBN 978-1-85315-869-8Google Scholar
- Bonhaus DW, Herman RC, Brown CM, Cao Z, Chang LF, Loury DN, Sze P, Zhang L, Hunter JC (1996) The beta 1 sodium channel subunit modifies the interactions of neurotoxins and local anesthetics with the rat brain IIA alpha sodium channel in isolated membranes but not in intact cells. Neuropharmacology 35:605–613PubMedCrossRefGoogle Scholar
- Leuwer M, Haeseler G, Hecker H, Bufler J, Dengler R, Aronson JK (2004) An improved model for the binding of lidocaine and structurally related local anaesthetics to fast-inactivated voltage-operated sodium channels, showing evidence of cooperativity. Br J Pharmacol 141:47–54PubMedCrossRefGoogle Scholar
- Wade AG (2008) A randomized, double-blind, parallel-group, placebo-controlled, multiple-dose study of the efficacy of Strepsils lozenges in the relief of acute sore-throat. Royal Society of Medicine Press, London. ISBN 978-1-85315-869-8Google Scholar