Wang G K, Vladimirov M, Quan C, Mok W M, Thalhammer J G, Anthony D C
Department of Anesthesia, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Anesthesiology. 1996 Dec;85(6):1386-94. doi: 10.1097/00000542-199612000-00020.
Neurolytic agents such as phenol (5% to 10%) and absolute alcohol have long been used clinically to destroy the pathogenic nerve regions that manifest pain. Both phenol and alcohol are highly destructive to nerve fibers. However, these agents exert only weak local anesthetic effects and therefore are difficult to administer to alert patients without pain. This report describes a tetracaine derivative that displays both local anesthetic and neurolytic properties. Studies with such a compound may lead to the design of neurolytic agents that are more effective and more easily administered than phenol and alcohol.
A tetracaine derivative, N-butyl tetracaine quaternary ammonium bromide, was synthesized, and its ability to elicit sciatic nerve block of sensory and motor functions in vivo was tested in rats. A single dose of 0.1 ml N-butyl tetracaine at 37 mM was injected into the sciatic notch. Transverse sections of treated sciatic nerves were subsequently examined to determine the neurolytic effect of this drug. Finally, the local anesthetic properties of N-butyl tetracaine were studied in vitro; both tonic inhibition and use-dependent inhibition of Na+ currents in neuronal GH3 cells were characterized under whole-cell voltage-clamp conditions.
N-butyl tetracaine at 37 mM (equivalent to 1.11% tetracaine-hydrochloric acid concentration) elicited prolonged sciatic nerve block of the withdrawal response to noxious pinch in rats for more than 2 weeks. The withdrawal response was fully restored after 9 weeks. Parallel to sensory block, motor functions of the hind legs were similarly blocked by this drug. Morphologic examinations 3 and 5 weeks after a single injection of drug revealed degeneration of many sciatic nerve fibers, consistent with the results of functional tests. Finally, N-butyl tetracaine was found to be a potent Na+ channel blocker in vitro. It produced strong tonic and use-dependent inhibition of Na+ currents with a potency comparable to that of tetracaine.
A single injection of N-butyl tetracaine produces ultralong sciatic nerve block in rats. This compound possesses both local anesthetic and neurolytic properties and may prove useful as a neurolytic agent in pain management.
诸如苯酚（5%至10%）和无水乙醇等神经破坏剂长期以来一直用于临床，以破坏引发疼痛的致病神经区域。苯酚和乙醇对神经纤维均具有高度破坏性。然而，这些药剂仅具有微弱的局部麻醉作用，因此难以用于清醒且无痛的患者。本报告描述了一种具有局部麻醉和神经破坏特性的丁卡因衍生物。对这类化合物的研究可能会促成设计出比苯酚和乙醇更有效且更易于给药的神经破坏剂。
合成了一种丁卡因衍生物，即N-丁基丁卡因溴化季铵盐，并在大鼠体内测试了其引发坐骨神经感觉和运动功能阻滞的能力。将37 mM的0.1 ml N-丁基丁卡因单剂量注射到坐骨切迹中。随后检查处理后的坐骨神经横切片，以确定该药物的神经破坏作用。最后，在体外研究了N-丁基丁卡因的局部麻醉特性；在全细胞膜片钳条件下，对神经元GH3细胞中Na+电流的强直抑制和使用依赖性抑制进行了表征。
37 mM的N-丁基丁卡因（相当于1.11%盐酸丁卡因浓度）使大鼠对有害捏夹的退缩反应的坐骨神经阻滞延长超过2周。9周后退缩反应完全恢复。与感觉阻滞平行，该药物同样阻断了后腿的运动功能。单次注射药物后3周和5周的形态学检查显示许多坐骨神经纤维发生变性，与功能测试结果一致。最后，发现N-丁基丁卡因在体外是一种有效的Na+通道阻滞剂。它对Na+电流产生强烈的强直和使用依赖性抑制，其效力与丁卡因相当。
单次注射N-丁基丁卡因可在大鼠中产生超长的坐骨神经阻滞。该化合物具有局部麻醉和神经破坏特性，可能被证明是疼痛管理中一种有用的神经破坏剂。
