Buchholz Vanessa, Leuwer Martin, Ahrens Jörg, Foadi Nilufar, Krampfl Klaus, Haeseler Gertrud
Clinic for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2009 Aug;380(2):161-8. doi: 10.1007/s00210-009-0416-x. Epub 2009 Apr 15.
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.
治疗咽喉痛的含片可缓解口腔炎症时的不适。目前，这种作用尚未得到充分解释。在此，我们研究了一种观点，即治疗咽喉痛的药物制剂中的关键成分，通常被视为防腐剂，可能具有钠通道阻断作用，即类似局部麻醉剂的作用。我们在体外研究了己基间苯二酚、戊基甲酚和二氯苄醇对在HEK 293细胞中异源表达的电压门控神经元（Na(V)1.2）钠通道的影响。己基间苯二酚、戊基甲酚和二氯苄醇可逆地阻断去极化诱导的全细胞钠内向电流。在-150 mV时，半数最大阻断浓度（EC(50)）分别为23.1、53.6和661.6 microM。己基间苯二酚和戊基甲酚诱导的阻断在去极化电位下增加，并且在高频（100 Hz）施加的去极化脉冲序列期间具有使用依赖性，这表明两种药物与通道的失活构象结合更紧密。己基间苯二酚和戊基甲酚对失活状态的亲和力估计分别为1.88和35 microM。在阻断钠内向电流方面，己基间苯二酚和戊基甲酚的效力比局部麻醉剂利多卡因高10 - 20倍。两种药物在去极化膜电位或高频放电条件下均表现出增强的作用。
