O'Shaughnessy C T, Aram J A, Lodge D
Department of Physiology, Royal Veterinary College, London, U.K.
Epilepsy Res. 1988 Sep-Oct;2(5):294-301. doi: 10.1016/0920-1211(88)90037-x.
It has been suggested that endogenous chemical substances such as adenosine, released during a seizure attack, may act as anticonvulsants in vivo. To further investigate this putative role, we have tested adenosine and stable adenosine analogues for anticonvulsant activity in vitro against ictal-like epileptiform activity induced by the removal of magnesium ions from medium superfusing wedges and slices of rat neocortex. Purinoceptor agonists attenuated such burst activity with a potency profile of L-phenylisopropyl-adenosine greater than 2-chloroadenosine greater than adenosine, suggesting that their anticonvulsant actions were mediated via the A1 adenosine receptor sub-type. Adenosine exerted no apparent effect on responses to agonists acting at glutamate receptor sub-types, implying no direct postsynaptic activity at glutamatergic synapses. Adenosine receptor antagonists, the methylxanthines (3-isobutyl-1-methylxanthine greater than theophylline) markedly enhanced established epileptiform activity and reversed the anticonvulsant action of adenosine. The selectivity of this reversal was demonstrated by the lack of effect of methylxanthines on pentobarbitone-induced inhibitions of epileptiform bursts. When added to a normal medium containing 1 mM magnesium, the methylxanthines were unable to induce long-lasting ictal-like epileptiform activity.
有人提出，内源性化学物质如腺苷在癫痫发作时释放，可能在体内起到抗惊厥作用。为进一步研究这一假定作用，我们测试了腺苷及稳定的腺苷类似物在体外对从灌注大鼠新皮质楔形切片和薄片的培养基中去除镁离子所诱发的癫痫样发作活动的抗惊厥活性。嘌呤受体激动剂减弱了此类爆发性活动，其效力顺序为L-苯基异丙基腺苷大于2-氯腺苷大于腺苷，这表明它们的抗惊厥作用是通过A1腺苷受体亚型介导的。腺苷对作用于谷氨酸受体亚型的激动剂的反应没有明显影响，这意味着在谷氨酸能突触处没有直接的突触后活性。腺苷受体拮抗剂甲基黄嘌呤（3-异丁基-1-甲基黄嘌呤大于茶碱）显著增强了已确立的癫痫样活动，并逆转了腺苷的抗惊厥作用。甲基黄嘌呤对戊巴比妥诱导的癫痫样爆发抑制作用缺乏影响，证明了这种逆转的选择性。当添加到含有1 mM镁的正常培养基中时，甲基黄嘌呤无法诱导持久的癫痫样发作活动。
