Velísková J, Velísek L, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY USA.
Epilepsia. 1996 Aug;37(8):718-22. doi: 10.1111/j.1528-1157.1996.tb00641.x.
To determine whether seizures have age-specific features, we studied the role of gamma-aminobutyric acidB (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days).
We used a GABAB receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABAB receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).
Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABAB receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.
The differences in the age-specific action of the GABAB agonist and antagonist suggest the different GABAB receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.
为了确定癫痫发作是否具有年龄特异性特征，我们研究了γ-氨基丁酸B（GABAB）传递在不同年龄（出生后9、15、30和60天）大鼠中的作用。
我们在戊四氮（PTZ）诱导的阵挛性和强直-阵挛性癫痫发作模型（皮下注射100mg/kg）中使用了GABAB受体激动剂巴氯芬（腹腔注射2或5mg/kg）和GABAB受体拮抗剂CGP 35348（腹腔注射100或600mg/kg）。
虽然巴氯芬在大多数动物中具有抗惊厥作用，而CGP 35348具有促惊厥作用，但这些药物的有效性存在明显的年龄相关差异，并且拮抗剂在成年动物中具有一定的抗惊厥活性。此外，与强直-阵挛性癫痫发作相比，作用于GABAB受体的这两种药物在阵挛性癫痫发作中的作用模式不同。
GABAB激动剂和拮抗剂年龄特异性作用的差异表明不同的GABAB受体亚群可能介导药物效应。结果表明，在开发过程中必须测试假定的抗癫痫药物（AEDs），因为不可能从成年动物的研究中推断出年龄特异性的抗惊厥作用。
