Charles University, Third Medical School, Department of Normal, Pathological and Clinical Physiology, Ke Karlovu 4, CZ-12000 Prague 2, Czech Republic.
Pharmacol Rep. 2010 Jan-Feb;62(1):62-7. doi: 10.1016/s1734-1140(10)70243-7.
Adenosine may represent an endogenous anticonvulsant in the brain. This study focused on the possible anticonvulsant action of an adenosine agonist, 2-chloroadenosine, against cortical epileptic afterdischarges (ADs) in immature rats. Three age groups of rat pups with implanted electrodes were studied: 12-, 18- and 25-days-old. The compound, 2-chloroadenosine, was injected after the first successful stimulation at doses of 1, 4 or 10 mg/kg intraperitoneally, and stimulation at the same intensity was repeated three more times. Movements directly elicited by stimulation, as well as clonic seizures accompanying electroencephalography (EEG) ADs, were markedly suppressed in only the 18-day-old animals. The effects in the 12- and especially the 25-day-old rats were moderate. The duration of the ADs decreased in all three age groups with 2-chloroadenosine treatment, and the shortest AD duration was seen in the treated, 12-day-old rats. The AD suppression also lasted longer in this age group than it did in the older animals. After a brief suppression of the second AD, the treated, 25-day-old group exhibited a significant AD rebound during the third and fourth stimulations. Taken together, our data show that 2-chloroadenosine exhibits an anticonvulsant effect that is dose- and age-dependent.
腺苷可能是大脑中的内源性抗惊厥剂。本研究集中研究了一种腺苷激动剂 2-氯腺苷对未成熟大鼠皮质癫痫后放电(AD)的可能抗惊厥作用。研究了三组植入电极的大鼠幼仔:12、18 和 25 天大。在第一次成功刺激后,以 1、4 或 10mg/kg 的剂量腹膜内注射该化合物 2-氯腺苷,并重复三次以相同强度进行刺激。仅在 18 天大的动物中,直接由刺激引起的运动以及脑电图(EEG)AD 伴随的阵挛性发作明显受到抑制。在 12 天和特别是 25 天大的大鼠中,效果适中。所有三个年龄组的 AD 持续时间均随 2-氯腺苷治疗而减少,而在接受治疗的 12 天大的大鼠中 AD 持续时间最短。在该年龄组中,AD 抑制作用的持续时间也比在较年长的动物中更长。在第二次 AD 短暂抑制后,接受治疗的 25 天大的组在第三次和第四次刺激期间表现出明显的 AD 反弹。总的来说,我们的数据表明 2-氯腺苷表现出剂量和年龄依赖性的抗惊厥作用。