Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis.
Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis.
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钾 M 电流激活剂在两种脑炎大鼠模型中具有抗惊厥作用。
DOI：
10.1016/j.ejphar.2006.10.025
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发表时间：
2007
影响因子：
5
通讯作者：
Koob,GeorgeF
中科院分区：
文献类型：
--
作者：
Solbrig,MarylouV;Adrian,Russell;Wechsler,StevenL;Koob,GeorgeF
海马中的阿片系统调节兴奋性，κ阿片在抗惊厥保护中起作用，但其作用机制尚不完全清楚。我们研究了阿片类和非阿片类药物的能力，重叠的离子机制和行动类似的κ阿片激动剂，阻断癫痫发作的大鼠模型，由于博尔纳病病毒和单纯疱疹病毒1型脑炎。纳曲吲哚，δ拮抗剂，因此是κ阿片样物质保留剂，（10 mg/kg s.c.）阻断模型中自发和纳洛酮（阿片拮抗剂）诱导的癫痫发作，但产生类似于阿片戒断的躯体体征。考虑到海马中δ拮抗剂以及κ阿片激动剂增强钾M电流（IM），我们测试了IM增强剂氟吡汀的作用。氟吡汀（20 mg/kg i. p.）在Borna和疱疹感染的大鼠中预防癫痫发作，没有戒断、张力减退或镇静的迹象。结果支持阿片类药物和非阿片类药物在调节病毒性脑炎引起的危重疾病中纳洛酮诱导的癫痫发作以及类比阿片类药物戒断癫痫发作中的疗效。
Opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. We examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to Borna Disease virus and Herpes Simplex Virus Type-1. Naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s.c.) blocked spontaneous and naloxone (opioid antagonist)-induced seizures in the models, but produced somatic signs similar to opioid withdrawal. Given that delta antagonists as well as kappa opioid agonists in hippocampus enhance potassium M currents (IM), we tested the effect of the IMaugmenter flupirtine. Flupirtine (20 mg/kg i.p.) prevented seizures in Borna and herpes infected rats, without signs of withdrawal, hypotonia or sedation. The results support the efficacy of opioid and nonopioid drugs in modulating naloxone-induced seizures in critical illness due to viral encephalitis and by analogy, opioid withdrawal seizures.