Stringer Janet L, Aribi Ahmed M
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
Epilepsy Res. 2002 Dec;52(2):129-37. doi: 10.1016/s0920-1211(02)00214-0.
Gabapentin (GBP) has been shown to reduce paired-pulse inhibition in the dentate gyrus of the urethane-anesthetized rat, which is a proconvulsant effect, and to shorten the afterdischarge duration, which is an antiepileptic effect. The mechanism by which GBP exerts these effects is not known, but a number of possibilities have been proposed. Here we tested the ability of vigabatrin (VGB), a GABA transaminase inhibitor, and SKF89976A, a selective GAT-1 blocker, to alter the effectiveness of GBP in the dentate gyrus in urethane-anesthetized adult Sprague-Dawley rats. VGB, alone at 100 mg/kg, had no effect on the evoked potentials or paired-pulse inhibition in the dentate gyrus, but did block lengthening of the afterdischarge. Pretreatment with VGB had no effect on the ability of GBP to reduce paired-pulse inhibition, but blocked the effect of GBP on seizure duration. SKF89976A, alone at 10 mg/kg, increased paired-pulse inhibition and blocked the lengthening of the afterdischarge in the seizure model. Pretreatment with SKF89976A had no effect on the actions of GBP on either paired-pulse inhibition or seizure duration. These results suggest that the action of GBP is not mediated through an inhibition of the GAT-1 transporter and probably not through an increase in basal levels of GABA. The data also suggest that the combination of VGB and GBP may be clinically less effective than the use of GBP alone.
加巴喷丁（GBP）已被证明可降低乌拉坦麻醉大鼠齿状回的双脉冲抑制，这是一种促惊厥作用，还可缩短放电后持续时间，这是一种抗癫痫作用。GBP发挥这些作用的机制尚不清楚，但已提出了多种可能性。在此，我们测试了γ-乙烯基-γ-氨基丁酸（VGB，一种γ-氨基丁酸转氨酶抑制剂）和SKF89976A（一种选择性γ-氨基丁酸转运体1（GAT-1）阻断剂）改变GBP对乌拉坦麻醉的成年Sprague-Dawley大鼠齿状回作用效果的能力。单独使用100mg/kg的VGB对齿状回的诱发电位或双脉冲抑制没有影响，但确实能阻止放电后持续时间的延长。用VGB预处理对GBP降低双脉冲抑制的能力没有影响，但能阻断GBP对癫痫发作持续时间的作用。单独使用10mg/kg的SKF89976A可增加双脉冲抑制，并在癫痫模型中阻断放电后持续时间的延长。用SKF89976A预处理对GBP在双脉冲抑制或癫痫发作持续时间方面的作用没有影响。这些结果表明，GBP的作用不是通过抑制GAT-1转运体介导的，可能也不是通过增加γ-氨基丁酸的基础水平介导的。数据还表明，VGB和GBP联合使用在临床上可能不如单独使用GBP有效。
