A combination of topical antiseptics for the treatment of sore throat blocks voltage-gated neuronal sodium channels.

Abstract

Amylmetacresol and dichloro-benzylalcohol are ingredients of lozenges used for the treatment of sore throat. In a former in vitro study, a local anaesthetic-like effect of these substances has been described. Since amylmetacresol and dichloro-benzylalcohol are co-administered in over-the-counter lozenges, the intention of this study is to evaluate the in vitro effects of the combination of these compounds on the voltage-gated sodium channel. We analysed the block of inward sodium currents induced by the combination of amylmetacresol, dichloro-benzylalcohol and the local anaesthetic lidocaine. Tonic and use-dependent block and effects on the inactivated channel state of the neuronal sodium channel were examined. Therefore, the α-subunit of the voltage-gated NaV1.2 sodium channel was heterologously expressed in HEK 293 cells in vitro. Inward sodium currents were investigated in the whole-cell configuration of the patch-clamp technique. The combination of amylmetacresol and dichloro-benzylalcohol and the combination of amylmetacresol and lidocaine induced a block of resting and inactivated sodium channels both displaying a pronounced block at the inactivated channel state. In addition, the combination of all three compounds also resulted in a voltage-dependent block of inward sodium currents. While use-dependent block by co-application of amylmetacresol and dichloro-benzylalcohol was moderate (<20 %), lidocaine and amylmetacresol induced a robust use-dependent block (up to 50 %). This study demonstrates local anaesthetic-like effects of a combination of amylmetacresol and dichloro-benzylalcohol as established ingredients of lozenges. In the presence of amylmetacresol, dichloro-benzylalcohol and lidocaine, a prominent block of inward sodium currents is apparent.

• Authors: Nilufar Foadi, Regina Campos de Oliveira, Vanessa Buchholz, Carsten Stoetzer, Florian Wegner, Igor Pilawski, Gertrud Haeseler, Martin Leuwer, Jörg Ahrens
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 387 Issue 10 Pg. 991-1000 (Oct 2014) ISSN: 1432-1912 [Electronic] Germany
• PMID: 25012093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Local
• Anti-Infective Agents, Local
• Benzyl Alcohols
• Cresols
• NAV1.2 Voltage-Gated Sodium Channel
• Sodium Channel Blockers
• amylmetacresol
• dichlorobenzyl alcohol
• Lidocaine

Topics

• Administration, Topical
• Anesthetics, Local (administration & dosage)
• Anti-Infective Agents, Local (administration & dosage)
• Benzyl Alcohols
• Cresols (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• HEK293 Cells
• Humans
• Lidocaine (administration & dosage)
• NAV1.2 Voltage-Gated Sodium Channel (physiology)
• Neurons (drug effects, physiology)
• Pharyngitis (drug therapy)
• Sodium Channel Blockers (administration & dosage)