Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
J Neural Transm (Vienna). 2010 Nov;117(11):1269-77. doi: 10.1007/s00702-010-0465-9. Epub 2010 Aug 31.
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.
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。