Partitioning of anesthetic to bio-molecule and thermodynamic activity

1.采用顶空进样气相色谱法测定了挥发性麻醉药的水/气、辛醇/水分配系数。2.测定了局部麻醉药丁卡因在含有不同浓度二肉豆蔻酰磷脂酰甘油（DMPG）的标准缓冲溶液中的紫外光谱。随着DMPG浓度的增加，光谱峰向短波方向移动。本文导出了丁卡因在DMPG膜中的光谱和丁卡因在缓冲液和DMPG膜之间的分配系数的测定公式。结果与讨论：（1）测定了丁卡因在DMPG膜中的紫外光谱，并通过改变膜浓度来估算其分配系数。（2）低温下，固-胶分配系数（S-G）降低，而液晶分配系数（L-C）保持不变。随着温度的降低，Zr（7）与S-G之间的分配系数差增大，麻醉效力增加。目前的结果成功地解释了局部麻醉剂效力的温度依赖性的悖论。（3）在相变温度以下，pH值对丁卡因在膜中的紫外光谱有影响，而在相变温度以上，pH值对丁卡因在膜中的紫外光谱无影响。在转变温度以上，丁卡因分子深深地渗透到膜中，从而免受外部pH变化的影响。（4）不带电荷的丁卡因在分配过程中体积变化不明显。压力的挤出效应不能解释麻醉的压力逆转。

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.