Liptáková S, Velísek L, Velísková J, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.
Epilepsia. 2000 Jul;41(7):788-93. doi: 10.1111/j.1528-1157.2000.tb00244.x.
To determine the effects of a newly synthesized epalon, ganaxolone (GNX), on primarily generalized seizures in rats of various ages during development. Epalons are classified as neuroactive steroids that interact at unique site of the GABAA receptor-Cl- channel complex in the central nervous system.
Sprague-Dawley male rats were used at 9, 15, 30, and 60 postnatal days (PN). GNX dissolved in 2-hydroxypropylbeta-cyclodextrine was administered intraperitoneally in different doses at various time points before flurothyl testing. The incidence and threshold of clonic and tonic-clonic flurothyl seizures were evaluated. Behavioral changes were also assessed.
In all age groups, the effects of GNX were dose dependent and more prominent 10 min after its administration. In PN 60 and PN 30 rats, GNX had dose-dependent anticonvulsant effects; tonic-clonic seizures were more sensitive to GNX treatment than clonic seizures. In PN 15 and PN 9 rats, GNX demonstrated dose-and time-dependent anticonvulsant effects against both types of flurothyl-induced seizures. GNX was more effective in PN 15 rats than in other age groups, but at doses that altered motor behavior.
GNX has anticonvulsant effects against flurothylinduced seizures in all age groups tested. Its effects are more prominent in the two younger age groups, especially in PN 15 rats, but are associated with motor side effects.
确定新合成的依帕隆——加奈索酮（GNX）对发育过程中不同年龄大鼠原发性全身性癫痫发作的影响。依帕隆属于神经活性甾体，可作用于中枢神经系统中GABAA受体 - 氯离子通道复合物的独特位点。
选用出生后9天、15天、30天和60天的雄性Sprague-Dawley大鼠。在进行三氟乙烷测试前的不同时间点，腹腔注射溶解于2-羟丙基-β-环糊精的不同剂量GNX。评估阵挛性和强直阵挛性三氟乙烷诱发癫痫发作的发生率和阈值。同时评估行为变化。
在所有年龄组中，GNX的作用呈剂量依赖性，给药后10分钟作用更显著。在出生后60天和30天的大鼠中，GNX具有剂量依赖性抗惊厥作用；强直阵挛性发作比阵挛性发作对GNX治疗更敏感。在出生后15天和9天的大鼠中，GNX对两种类型的三氟乙烷诱发的癫痫发作均表现出剂量和时间依赖性抗惊厥作用。GNX在出生后15天的大鼠中比在其他年龄组中更有效，但会改变运动行为。
GNX对所有测试年龄组的三氟乙烷诱发的癫痫发作均有抗惊厥作用。其作用在两个较年轻的年龄组中更显著，尤其是在出生后15天的大鼠中，但与运动副作用相关。
