D'Hooge R, Pei Y Q, De Deyn P P
Laboratory of Neurochemistry and Behavior, Born-Bunge Foundation, University of Antwerp, Belgium.
Neurosci Lett. 1993 Jul 23;157(2):123-6. doi: 10.1016/0304-3940(93)90718-z.
Increased levels of the endogenous convulsant guanidinosuccinate (GSA) might contribute to the epileptic symptomatology presenting in patients with renal failure. Little is known, however, about the underlying epileptogenic mechanism of guanidinosuccinate-induced convulsions. In this paper, we present pharmacological evidence for a direct excitatory action of this compound. In particular, the close involvement of N-methyl-D-aspartate (NMDA) receptors in the pathogenesis of GSA-induced generalized convulsions is suggested. GSA potentiated NMDA-induced convulsions significantly, but not L-glutamate- or kainate-induced convulsions. Conversely, and in addition, NMDA receptor antagonists, like D(-)-2-amino-5-phosphonovalerate, CGP 37849 [DL)-(E)-2-amino-4-methyl-5-phosphono-3-pentenoate] or ketamine (but not kynurenate), blocked the convulsions induced by i.c.v. injection of GSA dose dependently whereas anti-epileptic drugs, like carbamazepine, diazepam, phenobarbital or valproate, only abolished the tonic extension phase of these convulsions. Thus, NMDA receptors appear to be involved, at least partly, in GSA-induced convulsions.
内源性惊厥剂胍基琥珀酸（GSA）水平升高可能导致肾衰竭患者出现癫痫症状。然而，关于胍基琥珀酸诱发惊厥的潜在致痫机制却知之甚少。在本文中，我们提供了该化合物直接兴奋作用的药理学证据。特别指出，N-甲基-D-天冬氨酸（NMDA）受体密切参与胍基琥珀酸诱发的全身性惊厥的发病机制。胍基琥珀酸显著增强NMDA诱发的惊厥，但不增强L-谷氨酸或海人藻酸诱发的惊厥。相反，此外，NMDA受体拮抗剂，如D-（-）-2-氨基-5-磷酸戊酸、CGP 37849[DL-（E）-2-氨基-4-甲基-5-磷酸-3-戊烯酸]或氯胺酮（但不包括犬尿氨酸），可剂量依赖性地阻断脑室内注射胍基琥珀酸诱发的惊厥，而抗癫痫药物，如卡马西平、地西泮、苯巴比妥或丙戊酸，仅消除这些惊厥的强直伸展期。因此，NMDA受体似乎至少部分参与了胍基琥珀酸诱发的惊厥。
