Ondrias K, Stasko A, Balgavý P
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Biochem Pharmacol. 1987 Nov 15;36(22):3999-4005. doi: 10.1016/0006-2952(87)90470-9.
The method of electron spin resonance spectroscopy of spin probes was used to determine the lowest concentrations of the local anaesthetics dibucaine and tetracaine exerting perturbations on synaptosome membranes. The perturbation depends on the temperature and the membrane depth, as well as on the concentration and the structure of the anaesthetics. Using spin labelled stearic acid at the 5th carbon position a negligible effect of the anaesthetics on the order parameter was found in the membrane both at 1 degree and 22 degrees, within the buffer concentration 0.01-10 mmol/l, but at 37 degrees and concentrations higher than 0.1 mmol/l the disordering effect was significant and of comparable efficiency for dibucaine and tetracaine. Employing stearic acid labelled at the 16th carbon position, disordering of the hydrocarbon core of the membrane caused by tetracaine or dibucaine was detected at 1 degree and 22 degrees, as well as at 37 degrees. The disordering effect occurred at buffer concentrations higher than 0.01 mmol/l for dibucaine, and higher than 0.1 mmol/l for tetracaine. At equal anaesthetic membrane concentrations and at the 16th carbon membrane depth, dibucaine was approximately twice as effective as tetracaine in perturbing synaptosomes. Tetracaine induced nonlamellar phases in the rat brain lipid membrane as detected by 31P NMR spectroscopy. The dynamic and structural perturbation effects of the local anaesthetics was found in that concentration range at which the anaesthetics influence various activities of biological membranes.
采用自旋探针电子自旋共振光谱法测定局部麻醉药丁卡因和丁哌卡因对突触体膜产生扰动的最低浓度。这种扰动取决于温度、膜深度，以及麻醉药的浓度和结构。在缓冲液浓度为0.01 - 10 mmol/L的情况下，使用在第5个碳位置自旋标记的硬脂酸，发现麻醉药在1℃和22℃时对膜中序参数的影响可忽略不计，但在37℃且浓度高于0.1 mmol/L时，丁卡因和丁哌卡因的无序化效应显著且效率相当。使用在第16个碳位置标记的硬脂酸，发现在1℃、22℃以及37℃时，丁哌卡因或丁卡因都会导致膜的烃核无序化。丁卡因在缓冲液浓度高于0.01 mmol/L时会出现无序化效应，而丁哌卡因则在高于0.1 mmol/L时出现。在麻醉药与膜的浓度相等且位于第16个碳的膜深度时，丁卡因在扰动突触体方面的效果约为丁哌卡因的两倍。通过31P核磁共振光谱法检测发现，丁哌卡因会在大鼠脑脂质膜中诱导非层状相。在麻醉药影响生物膜各种活性的浓度范围内，发现了局部麻醉药的动态和结构扰动效应。
