Anesthetic pharmacology of the mint extracts L-carvone and methyl salicylate

Introduction: Hydrocarbons with sufficient water solubility allosterically modulate anesthetic-sensitive ion channels. Mint extracts L-carvone and methyl salicylate water solubility exceeds modulation cutoff values for γ-amino butyric acid type A (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors, and type-2 voltage-gated sodium (Nav1.2) channels. We hypothesized that mint extracts modulate these channels at concentrations that anesthetize rats. Methods:Channels were expressed separately in frog oocytes and studied using 2-electrode voltage clamp techniques at drug concentrations up to 10 mM. Normalized current effects were fit to Hill equations. Mint compounds were formulated in a lipid emulsion and administered IV to rats. When unresponsive to the tail clamp, rats were exsanguinated, and plasma drug concentrations were measured. Results: Both mint compounds caused concentration-dependent inhibition of all channels except for methyl salicylate which inhibited GABAA receptors at l...引言：具有足够水溶性的烃类可变构调节麻醉敏感性离子通道。薄荷提取物中的L-香芹酮（L-carvone）与水杨酸甲酯（methyl salicylate）的水溶性，超过了γ-氨基丁酸A型（GABAA）受体、N-甲基-D-天冬氨酸（NMDA）受体以及2型电压门控钠（Nav1.2）通道的调制阈值。本研究假设，薄荷提取物可在使大鼠产生麻醉效应的浓度下对上述离子通道产生调制作用。 方法：将各离子通道分别在蛙卵母细胞中异源表达，采用双电极电压钳技术（2-electrode voltage clamp）开展研究，药物浓度最高设置为10 mM。将归一化电流效应拟合至希尔方程（Hill equations）。将薄荷类化合物制备为脂质乳剂后经静脉（intravenous, IV）给予大鼠。当大鼠对尾部夹刺激无反应时，对其实施放血并处死，并检测血浆中的药物浓度。 结果：两种薄荷类化合物均对所有离子通道产生浓度依赖性抑制作用，仅水杨酸甲酯对GABAA受体的抑制作用在[...]