Mattson R H, Petroff O A, Rothman D, Behar K
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Acta Neurol Scand Suppl. 1995;162:27-30. doi: 10.1111/j.1600-0404.1995.tb00496.x.
Vigabatrin is undoubtedly one of the most exciting anti-epilepsy drugs in use today. Many open and controlled clinical trials have confirmed that it is particularly effective in controlling partial epileptic seizures with or without secondary generalization. Vigabatrin acts to increase GABA levels in the presynaptic nerve terminal by inhibiting the activity of GABA-transaminase. There is no direct correlation between the blood or brain concentration of vigabatrin and its clinical effect, so monitoring vigabatrin levels is not predictive of patient response. However, it is possible to relate the activity of vigabatrin to levels of GABA in the brain, measured by nuclear magnetic resonance spectroscopy (NMRS). NMRS studies show that following administration of vigabatrin, brain concentrations of GABA rise to about 2-3 times their baseline values. This 'extra' GABA is held within the nerve terminal, and is only released during synaptic transmission. Although there appears to be a clear dose-response relationship up to 3 g/day, it is not well documented if higher doses result in proportionately higher brain GABA levels. This finding seems to support the results of clinical studies suggesting that the optimal dose of vigabatrin may be 3 g/day. There is also some evidence for a correlation between the concentration of GABA in the brain and the clinical outcome. Continuing investigations using NMRS aim to confirm these preliminary findings, and to determine the time course and extent of changes in brain GABA levels after vigabatrin administration.
氨己烯酸无疑是当今使用的最令人兴奋的抗癫痫药物之一。许多开放性和对照临床试验已证实，它在控制伴有或不伴有继发性全身性发作的部分性癫痫发作方面特别有效。氨己烯酸通过抑制γ-氨基丁酸转氨酶的活性来提高突触前神经末梢中的γ-氨基丁酸水平。氨己烯酸的血液或脑浓度与其临床效果之间没有直接关联，因此监测氨己烯酸水平并不能预测患者的反应。然而，通过核磁共振波谱法（NMRS）测量，可以将氨己烯酸的活性与脑中γ-氨基丁酸的水平联系起来。NMRS研究表明，服用氨己烯酸后，脑中γ-氨基丁酸的浓度会升至基线值的约2至3倍。这种“额外的”γ-氨基丁酸被保留在神经末梢内，仅在突触传递过程中释放。尽管在每日剂量达3克时似乎存在明显的剂量反应关系，但更高剂量是否会导致成比例更高的脑γ-氨基丁酸水平，目前尚无充分记录。这一发现似乎支持了临床研究结果，即氨己烯酸的最佳剂量可能为每日3克。也有一些证据表明脑中γ-氨基丁酸的浓度与临床结果之间存在关联。使用NMRS进行的持续研究旨在证实这些初步发现，并确定服用氨己烯酸后脑γ-氨基丁酸水平变化的时间进程和程度。
