Longo R, Domenici M R, Scotti de Carolis A, Sagratella S
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Life Sci. 1995;56(21):PL409-14. doi: 10.1016/0024-3205(95)00158-3.
The influence of the anticonvulsant felbamate has been tested on in vitro excitotoxicity induced by treatment of hippocampal slices with elevated concentrations of NMDA, AMPA and kainic acid. For comparison, the effects of the glutamate antagonist 7-chlorokynurenic acid and of the anticonvulsants pentobarbitone and lamotrigine, were also studied. Slice perfusion with 50 microM NMDA or 25 microM AMPA or 12 microM kainic acid produced within 30 min a disappearance or a pronounced irreversible amplitude reduction of the CA1 electrical synaptic responses. Slice perfusion with 1.2-1.6 mM felbamate or 100 microM lamotrigine significantly decreased the incidence of the irreversible disappearance of the CA1 electrical response induced by kainic acid. On the contrary, slice perfusion with the same concentrations of the drugs did not affect the irreversible disappearance of the CA1 electrical response induced by NMDA or AMPA. By contrast, slice perfusion with 100 microM of 7-chlorokynurenic acid significantly prevented the neurotoxic effects induced by both NMDA and kainic acid, while 100 microM of pentobarbitone failed to affect kainic acid-induced neurotoxicity. The different profile of neuroprotection elicited by felbamate with respect to reference drugs indicates that a different mechanism of action than antagonism of NMDA response or potentiation of GABA response underlies the neuroprotectant effects of felbamate.
已对抗惊厥药非氨酯对用高浓度N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和红藻氨酸处理海马切片所诱导的体外兴奋毒性的影响进行了测试。为作比较，还研究了谷氨酸拮抗剂7-氯犬尿氨酸以及抗惊厥药戊巴比妥和拉莫三嗪的作用。用50微摩尔/升NMDA或25微摩尔/升AMPA或12微摩尔/升红藻氨酸对切片进行灌流，在30分钟内会导致CA1电突触反应消失或出现明显的不可逆幅度降低。用1.2 - 1.6毫摩尔/升非氨酯或100微摩尔/升拉莫三嗪对切片进行灌流，可显著降低由红藻氨酸诱导的CA1电反应不可逆消失的发生率。相反，用相同浓度的这些药物对切片进行灌流，并不影响由NMDA或AMPA诱导的CA1电反应的不可逆消失。相比之下，用100微摩尔/升7-氯犬尿氨酸对切片进行灌流可显著预防由NMDA和红藻氨酸两者诱导的神经毒性作用，而100微摩尔/升戊巴比妥未能影响红藻氨酸诱导的神经毒性。与参比药物相比，非氨酯所引发的不同神经保护模式表明，非氨酯的神经保护作用是基于一种不同于NMDA反应拮抗或GABA反应增强的作用机制。
