Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults
Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults
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DOI：
10.1212/wnl.58.3.368
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发表时间：
2002-02-12
期刊：
影响因子：
9.9
通讯作者：
Hetherington, H
中科院分区：
文献类型：
--
作者：
Kuzniecky, R;Ho, S;Hetherington, H
背景：抗惊厥药物有多种作用机制。最近的体内MRS研究表明，大脑γ-氨基丁酸（GABA）的增加发生在人类某些抗惊厥药的管理。目的：研究托吡酯、加巴喷丁和拉莫三嗪对健康志愿者脑内GABA浓度的影响，并将GABA浓度与血药浓度进行相关性分析。研究方法：17名健康成年人被随机分配接受托吡酯，加巴喷丁，拉莫三嗪，并进行GABA测量使用4.1 T磁铁从13.5毫升的体积在枕区。GABA浓度和血清水平在急性单剂量的一种药物给药后3小时和6小时测量。此后，在4周内将药物滴定至目标剂量，并在第2周和第4周进行GABA测量。结果：与托吡酯治疗前相比，急性期脑GABA浓度升高70%。加巴喷丁组6小时GABA升高48%，拉莫三嗪组则无此变化。长期给药和一旦在4周时达到目标剂量，与基线相比，观察到所有三种药物（托吡酯46%，加巴喷丁25%，拉莫三嗪25%）的GABA显著升高。结论：这项研究表明，单剂量的托吡酯和加巴喷丁增加脑GABA浓度急性（小时）在健康个体，但所有药物在临床使用剂量增加脑GABA在4周。这些结果表明，抗惊厥药物的作用机制更复杂，可能是多种性质。
Background: Anticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral gamma-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. Objective: To investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. Methods: Seventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. Results: Cerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). Conclusion: This study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature.