Yamaguchi S, Donevan S D, Rogawski M A
Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 29892.
Epilepsy Res. 1993 Jul;15(3):179-84. doi: 10.1016/0920-1211(93)90054-b.
The anticonvulsant activities of a noncompetitive (GYKI 52466) and a competitive (NBQX) AMPA/kainate antagonist were compared in the maximal electroshock (MES) seizure test and various chemoconvulsant models. Both antagonists were protective in the MES and pentylenetetrazol tests. GYKI 52466 was also protective against seizures and lethality induced by 4-aminopyridine, kainate and AMPA, but not by NMDA, whereas NBQX was ineffective in these chemoconvulsant tests. Both GYKI 52466 and NBQX produced motor impairment at doses similar to those that were protective in the MES test. Under some circumstances, noncompetitive AMPA/kainate antagonists could offer advantages over competitive antagonists in seizure therapy. However, neurological toxicity is an obstacle to the potential clinical use of both classes of agents.
在最大电休克（MES）惊厥试验和各种化学惊厥模型中，比较了一种非竞争性（GYKI 52466）和一种竞争性（NBQX）AMPA/海人酸拮抗剂的抗惊厥活性。两种拮抗剂在MES和戊四氮试验中均具有保护作用。GYKI 52466对4-氨基吡啶、海人酸和AMPA诱导的惊厥和致死性也有保护作用，但对NMDA诱导的无效，而NBQX在这些化学惊厥试验中无效。GYKI 52466和NBQX在与MES试验中具有保护作用的剂量相似时均产生运动障碍。在某些情况下，非竞争性AMPA/海人酸拮抗剂在癫痫治疗中可能比竞争性拮抗剂具有优势。然而，神经毒性是这两类药物潜在临床应用的障碍。
