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2-氯腺苷对戊四氮诱导的未成熟大鼠癫痫发作的抗惊厥作用是由于激活 A1 腺苷受体。

Anticonvulsant action of 2-chloroadenosine against pentetrazol-induced seizures in immature rats is due to activation of A1 adenosine receptors.

机构信息

Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.

出版信息

J Neural Transm (Vienna). 2010 Nov;117(11):1269-77. doi: 10.1007/s00702-010-0465-9. Epub 2010 Aug 31.

Abstract

Potentiation of adenosinergic inhibitory modulation is one of possible strategies to develop new antiepileptic drugs. Nonspecific receptor agonist 2-chloroadenosine was tested against pentetrazol-induced convulsions in immature (7, 12, 18 and 25 days old) and adult rats. Doses of 1-15 mg/kg i.p. suppressed tonic phase of generalized tonic-clonic seizures (GTCS) in the two youngest groups, whereas GTCS were abolished in older rats. Minimal clonic seizures in 18-day and older rats were suppressed by high doses of 2-chloroadenosine. The role of A1 and A2A adenosine receptors was studied in 12- and 25-day-old rats. Action of an agonist of A1 receptors CCPA is similar to that of 2-chloroadenosine. An agonist of A2A receptors CGS 21680 exhibits an anticonvulsant action only in the dose-inducing catalepsy; an A2A antagonist ZM 241385 moderately suppressed tonic phase of GTCS only in 12-day-old animals. Anticonvulsant action of adenosine agonists is due to their effects on A1 receptors.

摘要

增强腺苷能抑制调节是开发新型抗癫痫药物的可能策略之一。非特异性受体激动剂 2-氯腺苷被测试用于对抗未成熟(7、12、18 和 25 天大)和成年大鼠的戊四唑诱导的惊厥。1-15mg/kg 的腹腔内剂量抑制了两个最年轻组的全身性强直阵挛性癫痫发作(GTCS)的强直性相,而在年龄较大的大鼠中 GTCS 则被消除。高剂量的 2-氯腺苷抑制了 18 天大的大鼠和更年长的大鼠的轻微阵挛性发作。在 12 天大和 25 天大的大鼠中研究了 A1 和 A2A 腺苷受体的作用。A1 受体激动剂 CCPA 的作用类似于 2-氯腺苷。A2A 受体激动剂 CGS 21680 仅在引起僵住的剂量下表现出抗惊厥作用;A2A 拮抗剂 ZM 241385 仅在 12 天大的动物中适度抑制 GTCS 的强直性相。腺苷激动剂的抗惊厥作用是由于它们对 A1 受体的作用。

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