title: 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.affiliation: Clinic for Anaesthesia and Critical Care Medicine; OE8050, Hannover Medical School, Carl-Neuberg-Str. 1, 30623, Hannover, Germany.
authors.forename: Nilufar
authors.initials: N
authors.lastname: Foadi
authors.forename: Regina Campos
authors.initials: RC
authors.lastname: de Oliveira
authors.forename: Vanessa
authors.initials: V
authors.lastname: Buchholz
authors.forename: Carsten
authors.initials: C
authors.lastname: Stoetzer
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
authors.forename: Igor
authors.initials: I
authors.lastname: Pilawski
authors.forename: Gertrud
authors.initials: G
authors.lastname: Haeseler
authors.forename: Martin
authors.initials: M
authors.lastname: Leuwer
authors.forename: Jörg
authors.initials: J
authors.lastname: Ahrens
mesh_terms: D000287:Administration, Topical; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage*; D001592:Benzyl Alcohols; D003408:Cresols / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D057809:HEK293 Cells; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010612:Pharyngitis / Q000188:drug therapy; D026941:Sodium Channel Blockers / Q000008:administration & dosage*
chemical_list: D000779:Anesthetics, Local; D000891:Anti-Infective Agents, Local; D001592:Benzyl Alcohols; D003408:Cresols; D062551:NAV1.2 Voltage-Gated Sodium Channel; D026941:Sodium Channel Blockers; C542912:amylmetacresol; C008396:dichlorobenzyl alcohol; D008012:Lidocaine