Potschka H, Feuerstein T J, Löscher W
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2000 Feb;361(2):200-5. doi: 10.1007/s002109900174.
The cyclic GABA analogue gabapentin (GBP), which recently has been marketed for treatment of epilepsy, is particularly effective against complex-partial seizures as occurring in temporal lobe epilepsy. In the present study, we compared the effects of GBP and its lactam analogue (GBP-L) in the amygdala kindling model of temporal lobe epilepsy. In fully kindled rats, GBP (50 mg/kg and 100 mg/kg i.p.) dose-dependently increased the threshold for focal seizures and inhibited the progression from focal to generalized seizures. This effect was not associated with any marked adverse effects. In contrast, GBP-L (10-50 mg/kg) induced myoclonic activity and generalized clonic seizures in kindled rats, demonstrating a striking qualitative difference between the two compounds. By comparison with non-kindled rats it was shown that kindling markedly enhanced the sensitivity of rats to the convulsant activity of GBP-L. The finding that the anticonvulsant efficacy of GBP is lost by lactam formation indicates that GBP and GBP-L differ in their mechanism(s) of action.
环状GABA类似物加巴喷丁（GBP）最近已上市用于治疗癫痫，对颞叶癫痫中出现的复杂部分性发作特别有效。在本研究中，我们比较了GBP及其内酰胺类似物（GBP-L）在颞叶癫痫杏仁核点燃模型中的作用。在完全点燃的大鼠中，GBP（腹腔注射50mg/kg和100mg/kg）剂量依赖性地提高局灶性癫痫发作阈值，并抑制从局灶性发作向全身性发作的进展。这种作用与任何明显的不良反应无关。相比之下，GBP-L（10-50mg/kg）在点燃的大鼠中诱发肌阵挛活动和全身性阵挛性发作，表明这两种化合物之间存在明显的质的差异。与未点燃的大鼠相比，发现点燃显著增强了大鼠对GBP-L惊厥活性的敏感性。GBP通过形成内酰胺而失去抗惊厥功效这一发现表明GBP和GBP-L的作用机制不同。
