Jayakumar A R, Sujatha R, Paul V, Puviarasan K, Jayakumar R
Department of Pharmacology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, Taramani, Chennai, India.
Brain Res Bull. 1999 Mar 1;48(4):387-94. doi: 10.1016/s0361-9230(99)00011-8.
The anticonvulsant drug Diazepam (DIA-2 mg/kg b. wt), the nitric oxide (NO) donor L-Arginine (L-Arg-2000 mg/kg b. wt) and the putative nitric oxide synthase (NOS) inhibitor N(G)-Nitro-L-Arginine methyl ester (L-NAME-50 mg/kg b. wt) were used to determine the role of endogenous NO on convulsions induced by picrotoxin (PCT-5 mg/kg b. wt) in rats. Rats given a convulsant dose of PCT (5 mg/kg b. wt) had convulsion and it suppresses the NOS activity and NO concentration in brain regions. The anticonvulsant L-Arg alone significantly increases the NO concentration and NOS activity in brain regions, but not diazepam. Whereas DIA, along with L-Arg, enhances the NO and NOS activity when compared to L-Arg alone. The combination of both OIA and L-Arg completely suppressed the convulsions. L-NAME alone had no effect to produce convulsions but it completely decreased NO concentration and NOS activity and potentiated the PCT convulsions. This was reverted by pre- and post treatment of DIA plus L-Arg indicating, the increased NO concentration and NOS activity in brain regions suppresses convulsions.
抗惊厥药物地西泮（DIA - 2毫克/千克体重）、一氧化氮（NO）供体L - 精氨酸（L - Arg - 2000毫克/千克体重）以及假定的一氧化氮合酶（NOS）抑制剂N（G）-硝基 - L - 精氨酸甲酯（L - NAME - 50毫克/千克体重）被用于确定内源性NO在大鼠中由印防己毒素（PCT - 5毫克/千克体重）诱导的惊厥中的作用。给予惊厥剂量PCT（5毫克/千克体重）的大鼠出现惊厥，并且它抑制脑区中的NOS活性和NO浓度。单独使用抗惊厥药L - Arg可显著增加脑区中的NO浓度和NOS活性，但地西泮无此作用。然而，与单独使用L - Arg相比，DIA与L - Arg一起可增强NO和NOS活性。DIA和L - Arg两者的组合完全抑制了惊厥。单独使用L - NAME对产生惊厥没有作用，但它完全降低了NO浓度和NOS活性，并增强了PCT惊厥。DIA加L - Arg的预处理和后处理可逆转这种情况，表明脑区中增加的NO浓度和NOS活性抑制了惊厥。
