The interaction between Mammalian Alkaloids and Anesthetics : Anesthetic Tolerance Associated with Alcohol Drinking and Prediction by Hair Analysis

关于与饮酒相关的麻醉耐受性，重点研究了与哺乳动物生物碱β-Carolines的相互作用的药理学背景和预测方法。一系列的结果被应用于麻醉效应变化和生物膜-药物相互作用的各种研究。1.某些β-Carolins作用于膜脂类，抑制局麻药和全麻药的膜流态化。这种抑制作用被它们的肝脏羟化代谢所消除。推测麻醉效果是通过与体内膜活性β-Caroline的相互作用而降低的。2.在新发展的高效液相色谱中，发现慢性酒精依赖者头发中的β-Caroline浓度显著增加。通过毛发分析可以预测与β-Carolines的强烈相互作用对麻醉的影响。3.局麻药显示反相色谱保留和膜-流态化活性关系…更多的臀部。基于膜流态化过程中的疏水相互作用，通过高效液相分析模拟麻醉效果的变化。4.将局麻药的疏水相互作用应用于输液气球，在注射后立即吸附局麻药，以降低流出液中局麻药的浓度。局麻药的膜流态化作用是在炎性酸性条件下诱导的，并被炎性过氧亚硝酸根抑制，与传统的假说相矛盾。6.用利多卡因离子季铵盐衍生物和立体结构--S(-)，R(-)-以及外消旋布比卡因和罗比卡因对神经细胞模型膜进行流态化。局麻药除与离子通道/受体蛋白的作用外，还与膜脂相互作用。7.麻醉相关药物，包括新型选择性β阻滞剂和酚类药物，表现出结构选择性的膜活性，提示膜流动性的改变是其作用机制之一。较少

Concerning anesthetic tolerance associated with drinking, the pharmacological background and prediction method were studied with focusing on the interaction with mammalian alkaloidal β-carbolines. A series of results were applied to various investigations on anesthetic effect change and biomembrane-drug interaction.1.Certain β-carbolines acted on membrane lipids to inhibit the membrane fluidization by local and general anesthetics. Such inhibition disappeared by their hepatic hydroxylation metabolism. It is speculated that anesthetic effects are decreased by the interaction with membrane-active β-carbolines increased in vivo by drinking.2.In the newly developed HPLC, the β-carboline concentrations in human scalp hair were found to significantly increase in chronic alcoholics. The potent interaction with β-carbolines to influence anesthesia may be predicted by hair analysis.3.Local anesthetics showed the reversed-phase chromatographic retention and membrane-fluidizing activity relations … More hips. Based on the hydrophobic interaction underlying membrane fluidization, the changes in anesthetic effects are simulated by HPLC analysis.4.The hydrophobic interaction of local anesthetics was applied to infusion balloons, which adsorbed local anesthetics immediately after injection to decrease their concentrations in effluents. Attention should be given to such adsorption so as not to influence clinical effects.5.The membrane-fluidizing effects of local anesthetics were induced under inflammatory acidic conditions and inhibited by inflammatory peroxynitrite, conflicting with the conventional hypothesis. The alternative mechanism should be theorized for the anesthetic failure in inflamed tissues.6.Nerve cell model membranes were fluidized by lidocaine ionic quaternary ammonium derivative and stereostructure-specifically fluidized by S(-)-,R(+)- and racemic bupivacaine and ropivacaine. The interaction with membrane lipids is responsible for the effects of local anesthetics in addition to that with ion channel/receptor proteins.7.Anesthetic-relating drugs, including new selective β-blockers and phenolic agents, showed the structure-selective membrane-activity, suggesting that the modification of membrane fluidity mechanistically contributes to their effects. Less