Topical antiseptics for the treatment of sore throat block voltage-gated neuronal sodium channels in a local anaesthetic-like manner.
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 (Na(V)1.2) 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 (EC(50)) at -150 mV were 23.1, 53.6 and 661.6 microM, 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 microM 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.
Buchholz
Vanessa
V
Clinic for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.
Leuwer
Martin
M
Ahrens
Jörg
J
Foadi
Nilufar
N
Krampfl
Klaus
K
Haeseler
Gertrud
G
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000494:pharmacology; D002460:Cell Line; D003408:Cresols / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006604:Hexylresorcinol / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010612:Pharyngitis / Q000188:drug therapy*; D051381:Rats; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015222:Sodium Channels; D014162:Transfection
D000779:Anesthetics, Local; D000891:Anti-Infective Agents, Local; D001592:Benzyl Alcohols; D003408:Cresols; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568251:SCN2A protein, human; C568253:Scn2A protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C542912:amylmetacresol; C008396:dichlorobenzyl alcohol; D008012:Lidocaine; D006604:Hexylresorcinol