Partitioning of anesthetic to bio-molecule and thermodynamic activity

麻醉剂对生物分子的分配和热力学活性

• 批准号: 12671512
• 负责人: KAMINOH Yoshiroh
• 金额: $ 1.98万
• 依托单位: HYOGO COLLEGE OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671512/
• 关键词: Anesthetic agent; partition coefficient; thermodynamic parameter; sevoflurane; tetracaine; UV spectrum; Gas chromatography; 熱力学的活量; プロポフォール

1.We measured water/gas, and octanol/water partition coefficients of volatile anesthetics by gas chromatography with head space sampler. The thermodynamic parameters were not determined because the results were scattering.2.The UV spectrum of local anesthetic, tetracaine, was measured n standard buffer solution with various concentration of dimylistoyl-phosphatidylglycerol (DMPG). The peak of spectrum shifted to the shorter wave leneth with increasing DMPG concentration. We derived the equation to determine thepartition coefficient of tetracaine between buffer and DMPG, and the spectrum of tetracaine in DMPG lembrane. The effect of temperature, pH and hydrostatic pressure were examined.Results and Discussion : (1)The UV spectrum of tetracaine in the DMPG membrane was measured, and partition coefficients were estimated by changing the membrane concentrations.(2)The partition, coefficient to solid-gel (S-G) decreased at low temperature, but that to liquid-crystalline (L-C) remained constant. When temperature decreased, the difference of partition coefficients between Zr(7and S-G enlarged, and the anesthetic potency increased. The current result successfully explained the paradox in the temperature dependence of local anesthetic potency.(3)The pH affected the UV spectra of tetracaine in membrane below the transition temperature, but did not above the transition temperature. Above the transition temperature, tetracaine molecule penetrated deeply into the membrane being protected from the external pH changes.(4)The volume change of uncharged tetracaine accompanied by the partitioning was not significant. The squeeze-out effect of pressure'failed to explain the pressure reversal of anesthesia.

1.采用顶空气相色谱进样器测定了挥发性麻醉药的水/气、辛醇/水分配系数。测定了局麻药丁卡因在不同浓度的二甲基磷脂酰甘油(DMPG)标准缓冲溶液中的紫外光谱。随着DMPG浓度的增加，谱峰向短波方向移动。推导了丁卡因在缓冲液和DMPG膜中的分配系数以及丁卡因在DMPG膜中的光谱。结果与讨论：(1)测定了丁卡因在DMPG膜中的紫外光谱，并通过改变膜浓度估算了丁卡因在膜中的分配系数：(2)低温下丁卡因对固体凝胶(S-G)的分配系数减小，而对液晶(L-C)的分配系数保持不变。随着温度的降低，分配系数与S-G的分配系数之差增大，麻醉效力增大。这一结果很好地解释了局部麻醉剂效价随温度变化的悖论。(3)pH值影响丁卡因在膜中的紫外光谱，但不影响膜中丁卡因的紫外光谱。在转变温度以上，丁卡因分子深入膜内，不受外界pH变化的影响。(4)未带电丁卡因在分配过程中体积变化不明显。压力挤出效应不能解释麻醉的压力反转.

项目成果

Yoshiroh Kaminoh, Chikara Tashiro, Hiroshi Kamaya: "Interaction of local anesthetics with DMPG membrane"Molecular and Basic Mechanisms of Anesthesia. Edited by Bernd W.Urban et al.. (In press).

Yoshiroh Kaminoh、Chikara Tashiro、Hiroshi Kamaya：“局麻药与 DMPG 膜的相互作用”麻醉的分子和基本机制。

Yoshiroh Kaminoh, Chikara Tashiro, Hiroshi Kamaya.: "Interaction of local anesthetics with DMPG membrane"Molecular and Basic Mechanisms of Anesthesia.Edited by Bernd W.Urban et al.. (In press).

Yoshiroh Kaminoh、Chikara Tashiro、Hiroshi Kamaya.：“局麻药与 DMPG 膜的相互作用”麻醉的分子和基本机制。Bernd W.Urban 等人编辑。（正在出版）。

Yoshiroh Kaminoh, Chikara Tashiro and Hiroshi Kamaya.: "Interaction of local anesthetics with DMPG membrane"Molecular and Basic Mechanisms of Anesthesia. Edited by Bernd W. Urban et al.. (in press).

Yoshiroh Kaminoh、Chikara Tashiro 和 Hiroshi Kamaya.：“局麻药与 DMPG 膜的相互作用”麻醉的分子和基本机制。