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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Interference with nitric oxide production and action potentiates the antiseizure efficacy of flurazepam.
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Interference with nitric oxide production and action potentiates the antiseizure efficacy of flurazepam.

机译：干扰一氧化氮的产生和作用可增强氟西epa的抗癫痫药功效。

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The effect of inhibiting "downstream" consequences of NMDA receptor stimulation with 7-nitroindazole, an inhibitor of the neuronal form of nitric oxide synthase (NOS), and methylene blue, an inhibitor of the nitric oxide (NO)-sensitive soluble guanylyl cyclase, on electrically precipitated tonic hindlimb extension in mice was studied. Moreover, the abilities of these compounds to potentiate the antiseizure efficacy of flurazepam were also examined. When administered alone, 7-nitroindazole (10.0-100 mg/kg) and methylene blue (1.0-100 mg/kg) did not share the ability of MK-801 (0.1 to 1.0 mg/kg) to antagonize electrically precipitated tonic hindlimb extension. However, doses of MK-801 (0.18 mg/kg), 7-nitroindazole (100 mg/kg), and methylene blue (10.0 and 100 mg/kg) that were devoid of apparent antiseizure efficacy by themselves potentiated the ability of flurazepam to antagonize electrically precipitated seizures. NMDA receptor antagonists cause neuronal toxicity, interfere with acquisition of spatial memory and induction of long-term potentiation in the hippocampal CA1 region, and precipitate psychoses in susceptible individuals. Thus, the development of both open-channel blockers of the NMDA receptor complex that can be administered in lower doses, and inhibitors of the "downstream" consequences of NMDA receptor-gated transient elevations of intraneuronal calcium ions as potential adjunctive antiseizure medications should be considered. Moreover, administration of these compounds with benzodiazepines may attenuate some of the neurotoxicity that may result from NMDA receptor antagonism.
机译：用一氧化氮合酶（NOS）的神经元形式的抑制剂7-硝基吲唑和一氧化氮（NO）敏感的可溶性鸟苷酸环化酶的抑制剂亚甲基蓝抑制NMDA受体刺激的“下游”后果的效果，对小鼠电沉淀补品后肢伸展进行了研究。此外，还检查了这些化合物增强氟西epa抗癫痫发作效力的能力。当单独给药时，7-硝基吲唑（10.0-100 mg / kg）和亚甲基蓝（1.0-100 mg / kg）不具有MK-801（0.1至1.0 mg / kg）拮抗电沉淀的补品后肢伸展的能力。但是，MK-801（0.18 mg / kg），7-硝基吲唑（100 mg / kg）和亚甲基蓝（10.0和100 mg / kg）的剂量本身没有明显的抗癫痫药作用，却增强了氟西epa的抗癫痫药治疗能力。拮抗电沉淀性癫痫发作。 NMDA受体拮抗剂引起神经元毒性，干扰海马CA1区空间记忆的获得和长期增强的诱导，并在易感个体中引起精神病。因此，应考虑开发两种可以以较低剂量给药的NMDA受体复合物的开放通道阻滞剂，以及作为潜在的辅助抗癫痫药物的NMDA受体引起的神经内钙离子瞬时升高的“下游”后果的抑制剂。 。此外，将这些化合物与苯二氮卓类药物一起给药可能会减弱由NMDA受体拮抗作用引起的某些神经毒性。

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