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Anticonvulsant Effect of Nitrous Oxide

一氧化二氮的抗惊厥作用

基本信息

批准号：
01570862
负责人：
OSAWA Masami
金额：
$ 1.28万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Nitrous oxide has a potent anticonvulsant action, but there are severa conflicting reports and the mechanism of anticonvulsant effect of nitrous oxide remains unknown.The purpose of this research is to investigate further the pharmacology of anticonvulsant action of nitrous oxide using various experimental models of induced convulsions. The following convulsion models were employed : 1) the maximum electroshock (MES) 2) drug induced convulsion : a) Iidocaine (local anesthetics), b) pentylenetetrazol and bicuculine (GABA antagonist), and c) 4-aminopyridine (potassium channel blocker).In the rat MES convulsion, severity of seizure was assessed by two indices : duration of tonic forelimb extention (TEF ; in sec), and motor seizure pattern (score). The control value for TFE was 11.9<plus-minus>1.1 (MEAN<plus-minus>SD) sec, and nitrous oxide suppressed it doseーdependently to 8.7<plus-minus>0.9sec, 6.3<plus-minus>0.9sec, 5.8<plus-minus>0.5sec, for 30%, 50% and 70% nitrous oxide, respectively … More . The effect of 70% nitrous oxide on the MES convulsion was approximately equivalent to a dose of diazepam of 5mg/Kg i. p., and both drugs acts synergFor drug induced convulsion, the change of the mean convulsion threshold dose of Iidocaine, pentyrentetrazol, bicuculine and 4-aminopyridine in air, by 70% nitrous oxide was examined. Nitrous oxide significantly increased the mean convulsion threshold dose of lidocaine, pentylenetetrazol, and bicuculine, but no anticonvulsant effect of nitrous oxide was seen on 4-aminopyridine convulsion. However, 4-aminopyridine convulsion was attenuated with diazepam (5mg/Kg i. p)Although we and others have reported on the acute tolerance of nitrous oxide up to now, in the present study, with MES and nitrous oxide administration up to 120 min, acute tolerance was not found.This study suggests that activation of brain inhibitory systems is the base for the anticonvulsant action of nitrous oxide. However it remains to be defined whether this is a direct (e. q. GABA receptor-channel) action of nitrous oxide, or not. The role of brain monoamines in the anticonvulsant ac ion of nitrous oxide should also be investigated. Less

一氧化二氮具有强效的抗惊厥作用，但存在多种相互矛盾的报道，一氧化二氮的抗惊厥作用机制仍不清楚。本研究的目的是利用各种诱发惊厥的实验模型进一步研究一氧化二氮抗惊厥作用的药理学。采用以下惊厥模型：1）最大电击（MES）2）药物诱导的惊厥：a）利多卡因（局部麻醉剂），b）戊四唑和荷包牡丹碱（GABA拮抗剂），和c）4-氨基吡啶（钾通道阻滞剂）。在大鼠MES惊厥中，通过两个指标评估癫痫发作的严重程度：持续时间强直前肢伸展（TEF；以秒为单位）和运动发作模式（分数）。 TFE 的控制值为 11.9±1.1（平均值±SD）秒，一氧化二氮将其剂量依赖性抑制至 8.7±0.9 秒、6.3±0.9 秒、5.8±0.5 秒，分别为 30%、50% 和 70% 一氧化二氮……更多。 70%一氧化二氮对MES惊厥的作用大约相当于地西泮剂量5mg/Kg i。 p.，并且两种药物具有协同作用。对于药物引起的惊厥，检测了70％一氧化二氮对空气中利多卡因、戊四氮、荷包牡丹碱和4-氨基吡啶的平均惊厥阈剂量的变化。一氧化二氮显着增加利多卡因、戊四氮和荷包牡丹碱的平均惊厥阈剂量，但一氧化二氮对4-氨基吡啶惊厥没有抗惊厥作用。然而，地西泮（5mg/Kg i. p）可减弱 4-氨基吡啶惊厥。虽然我们和其他人迄今为止已经报道了一氧化二氮的急性耐受性，但在本研究中，MES 和一氧化二氮给药长达 120 分钟，没有发现急性耐受性。这项研究表明，脑抑制系统的激活是一氧化二氮抗惊厥作用的基础。氧化物。然而，这是否是一氧化二氮的直接（例如 GABA 受体通道）作用仍有待确定。还应研究脑单胺在一氧化二氮的抗惊厥活性离子中的作用。较少的