Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy.
Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy.
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神经活性类固醇在经期癫痫大鼠模型中增强抗惊厥活性。
DOI：
10.1046/j.1528-1157.2001.10200.x
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发表时间：
2001
期刊：
影响因子：
5.6
通讯作者：
Rogawski,MA
中科院分区：
文献类型：
--
作者：
Reddy,DS;Rogawski,MA
目的：月经期癫痫的部分原因可能是由于内源性孕酮衍生的神经类固醇异孕酮的停药，增强γ -氨基丁酸（GABAA）受体介导的抑制作用。在本研究中，我们试图确定神经活性类固醇、苯二氮卓类药物、苯巴比妥（PB）和丙戊酸盐（VPA）的抗惊厥效力是否会在月经期癫痫大鼠模型中随着神经类固醇戒断而增加的癫痫易感性中发生改变。方法：在年轻成年雌性大鼠、长时间暴露于高水平孕酮（及其神经类固醇代谢物）的假妊娠大鼠和用5α -还原酶抑制剂非那雄胺治疗急性停药后24小时的假妊娠大鼠中，评估试验药物改变戊四唑（PTZ）惊厥活性的能力。试验药物的剂量相当于其ed50值的两倍，以保护年轻成年雌性大鼠免受PTZ诱导的慢性癫痫发作。结果：停药后异孕酮（5mg /kg, s.c）、孕酮（5mg /kg, s.c）、异四氢脱氧皮质酮（15mg /kg, s.c）、四氢脱氧皮质酮（10mg /kg, s.c）的抗惊厥活性增强34-127%。在神经类固醇戒断的动物中，PB （65 mg/kg, i.p）的抗惊厥活性也提高了24%。相反，地西泮（4mg /kg, i.p）、布雷他尼（0.106 mg/kg, i.p）和VPA （560mg /kg, i.p）的抗惊厥活性在神经类固醇戒断动物中降低或保持不变。结论：神经活性类固醇在停药后抗惊厥活性增强，支持使用此类药物治疗月经围期癫痫。
Purpose:Perimenstrual catamenial epilepsy may in part be due to withdrawal of the endogenous progesterone‐derived neurosteroid allopregnanolone that potentiates γ‐aminobutyric acidA(GABAA) receptor–mediated inhibition. Here we sought to determine whether the anticonvulsant potencies of neuroactive steroids, benzodiazepines, phenobarbital (PB), and valproate (VPA) are altered during the heightened seizure susceptibility accompanying neurosteroid withdrawal in a rat model of perimenstrual catamenial epilepsy.Methods:Test drugs were evaluated for their ability to alter the convulsant activity of pentylenetetrazol (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure to high levels of progesterone (and its neurosteroid metabolites), and in pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment with the 5α‐reductase inhibitor finasteride. Test drugs were administered at doses equivalent to twice their ED50values for protection against PTZ‐induced clonic seizures in naive young adult female rats.Results:The anticonvulsant activity of allopregnanolone (5 mg/kg, s.c.), pregnanolone (5 mg/kg, s.c.), allotetrahydrodeoxycorticosterone (15 mg/kg, s.c.), and tetrahydrodeoxycorticosterone (10 mg/kg, s.c.) were enhanced by 34–127% after neurosteroid withdrawal. The anticonvulsant activity of PB (65 mg/kg, i.p.) was also enhanced by 24% in neurosteroid‐withdrawn animals. In contrast, the anticonvulsant activity of diazepam (4 mg/kg, i.p.), bretazenil (0.106 mg/kg, i.p.), and VPA (560 mg/kg, i.p.) were reduced or unchanged in neurosteroid‐withdrawn animals.Conclusions:The anticonvulsant activity of neuroactive steroids is potentiated after neurosteroid withdrawal, supporting the use of such agents in the treatment of perimenstrual catamenial epilepsy.
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影响因子：
2.9
作者：
Devaud, LL;Fritschy, JM;Morrow, AL
通讯作者：
Morrow, AL
开发基于神经类固醇的新型精神药物。
影响因子：
--
作者：
D Samba Reddy;Shrinivas K. Kulkarni
通讯作者：
Shrinivas K. Kulkarni
发情周期对γ-氨基丁酸A受体复合物的神经类固醇效力的影响。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Finn,DA;Gee,KW
通讯作者：
Gee,KW
影响因子：
5.6
作者：
Monaghan, EP;Navalta, LA;Lee, DA
通讯作者：
Lee, DA
影响因子：
9.9
作者：
HERZOG, AG
通讯作者：
HERZOG, AG