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

哺乳动物生物碱与麻醉药之间的相互作用：与饮酒相关的麻醉耐受性和通过头发分析进行预测

基本信息

批准号：
15592145
负责人：
TSUCHIYA Hironori
金额：
$ 1.79万
依托单位：
Asahi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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

针对饮酒引起的麻醉耐受性，研究了饮酒引起麻醉耐受性的药理学背景和预测方法，重点研究了饮酒与哺乳动物体内β-咔啉类药物的相互作用。结果表明：1.某些β-咔啉类化合物作用于膜脂质，抑制局麻药和全麻药引起的膜流体化。这种抑制作用通过肝羟化代谢而消失。推测其麻醉作用可能与饮酒后体内增加的膜活性β-咔啉相互作用而降低。2.在新开发的HPLC中，发现慢性酒精中毒者头皮毛发中β-咔啉浓度显著增加。通过毛发分析可以预测局部麻醉药与β-咔啉类药物的相互作用对麻醉作用的影响 ...更多信息的臀部基于膜流化过程中的疏水相互作用，通过HPLC分析模拟了麻醉效果的变化。4.将局麻药的疏水相互作用应用于输液球囊，使其在注射后立即吸附局麻药，以降低流出液中的局麻药浓度。局部麻醉药的膜流化作用在炎性酸性条件下可被诱导，而在炎性过氧亚硝基阴离子条件下可被抑制，这与传统的假设不符。6.利多卡因离子型季铵衍生物流化神经细胞模型膜，S（-）-、R（+）-和外消旋布比卡因和罗哌卡因立体结构特异性流化神经细胞模型膜。7.麻醉相关药物，包括新的选择性β受体阻滞剂和酚类药物，表现出结构选择性的膜活性，表明改变膜流动性是其作用机制之一。少