ITS Paramedical College, Ghaziabad, India.
Indian J Pharmacol. 2009 Feb;41(1):41-6. doi: 10.4103/0253-7613.48890.
The present study describes the effect of nebivolol (NBV) either alone or in combination with lamotrigine (LTG) using increasing current electroshock seizures (ICES) model in mice.
Male albino mice of Swiss strain each weighing 18-30 g were used. Lamotrigine (Lamitor tablets, Torrent; 1.5 and 3.0 mg/kg) and NBV (Nebicard tablets, Torrent; 0.25 and 0.5 mg/kg) were suspended in 0.25% of carboxy methyl cellulose (CMC) in 0.9% saline and administered orally in volumes of 10 mg/kg. Control animals received an equivalent volume of 0.25% CMC in 0.9% saline suspension. The anticonvulsant effects of the drugs were measured using ICES model whereas cognitive behavior was measured by the spontaneous alternation behavior and grip-strength test. The biochemical estimation was done by measuring the lipid peroxidation and reduced glutathione (GSH).
Both NBV and LTG produced significantly enhanced seizure threshold (ST), decreased grip strength, inhibited lipid peroxidation, and increased brain GSH levels in acute and chronic dosages likened to control group, whereas there was no significant effect on alternation scores. The combination of NBV with LTG significantly potentiated the ST when compared to LTG.
Nebivolol showed antiepileptic effects in addition to its reported antihypertensive effect, which could be attributed to action of the two drugs through different mechanisms or due to drug interaction that may be pharmacodynamic or pharmacokinetic needing elucidation.
本研究描述了单独使用或联合使用比索洛尔(NBV)和拉莫三嗪(LTG)对雄性瑞士白化小鼠递增电流电休克发作(ICES)模型的影响。
使用体重为 18-30 克的雄性白化瑞士系小鼠。拉莫三嗪(Lamitor 片剂,Torrent;1.5 和 3.0mg/kg)和 NBV(Nebicard 片剂,Torrent;0.25 和 0.5mg/kg)悬浮在 0.9%生理盐水的 0.25%羧甲基纤维素(CMC)中,并以 10mg/kg 的体积口服给药。对照动物给予等体积的 0.25%CMC 在 0.9%生理盐水悬浮液中。使用 ICES 模型测量药物的抗惊厥作用,而通过自发交替行为和握力测试测量认知行为。通过测量脂质过氧化和还原型谷胱甘肽(GSH)来进行生化估计。
与对照组相比,NBV 和 LTG 均显著提高了 ST,降低了握力,抑制了脂质过氧化,并增加了脑 GSH 水平,无论是急性还是慢性剂量,而交替评分没有显著影响。与 LTG 相比,NBV 与 LTG 的联合使用显著增强了 ST。
除了其报道的降压作用外,比索洛尔还显示出抗癫痫作用,这可能归因于两种药物通过不同机制或由于药物相互作用的作用,可能是药效学或药代动力学需要阐明。