Snead O C
Department of Neurology, Childrens Hospital Los Angeles, University of Southern California, School of Medicine, Los Angeles, USA.
Pharmacol Biochem Behav. 1996 Jan;53(1):73-9. doi: 10.1016/0091-3057(95)00200-6.
Hydroxybutyric acid (GHB) is a naturally occurring compound that has the ability to induce generalized absence seizures possibly by GABAB-receptor-mediated mechanisms. The object of these experiments was to examine the effectiveness of a range of specific GABAB-receptor agonists and antagonists of varying specificity, as well as the specific GHB-receptor antagonist NCS 382, in two experimental animal models of generalized absence seizures: one in which the seizures are induced by GHB and the other in which the seizures are induced by administration of low-dose (20-mg/kg) pentylenetetrazole. All specific GABAB-receptor antagonists as well as the specific GHB-receptor antagonist produced blockade of experimental absence seizures in both models; pretreatment with GABAB-receptor agonists resulted in generalized absence status epilepticus lasting for hours. These data confirm the concept that specific GABAB-receptor antagonist activity confers antiabsence seizure activity, suggest that the same holds for specific GHB-receptor antagonists, and raise the possibility that both GHB- and GABAB-antagonist drugs have the potential to be useful therapeutic agents in generalized absence seizures.
羟基丁酸（GHB）是一种天然存在的化合物，它可能通过GABAB受体介导的机制诱发全身性失神发作。这些实验的目的是在两种全身性失神发作的实验动物模型中，研究一系列特异性不同的GABAB受体激动剂和拮抗剂以及特异性GHB受体拮抗剂NCS 382的有效性：一种模型中发作由GHB诱发，另一种模型中发作由低剂量（20毫克/千克）戊四氮给药诱发。在两种模型中，所有特异性GABAB受体拮抗剂以及特异性GHB受体拮抗剂均能阻断实验性失神发作；用GABAB受体激动剂预处理会导致持续数小时的全身性失神癫痫持续状态。这些数据证实了特异性GABAB受体拮抗剂活性具有抗失神发作活性这一概念，表明特异性GHB受体拮抗剂也同样如此，并增加了GHB拮抗剂和GABAB拮抗剂药物都有可能成为全身性失神发作有用治疗药物的可能性。
