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

作者：Foadi Nilufar; de Oliveira Regina Campos; Buchholz Vanessa; Stoetzer Carsten; Wegner Florian; Pilawski Igor; Haeseler Gertrud; Leuwer Martin; Ahrens Joerg^*

来源：Naunyn-Schmiedeberg's Archives of Pharmacology, 2014, 387(10): 991-1000.

DOI：10.1007/s00210-014-1016-y

• Sodium channels
• Voltage-operated
• Local anaesthetic
• Amylmetacresol
• Dichloro-benzylalcohol
• Lidocaine

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 alpha-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 (%26lt; 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.

• 出版日期2014-10