Talarek Sylwia, Fidecka Sylwia
Department of Pharmacodynamics, Medical University School, Staszica 4, PL 20-081 Lublin, Poland.
Pol J Pharmacol. 2003 Mar-Apr;55(2):181-91.
The influence of nitric oxide (NO) on anticonvulsant activity of diazepam and clonazepam was examined in the pentetrazole- and electroshock-induced seizure models in mice. Protective efficacy of the threshold dose of diazepam against pentetrazole-induced clonic and tonic seizures, and death was significantly increased by NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) while 7-nitroindazole (7-NI) was slightly less effective. The above intensifying effect of L-NAME on antiepileptic activity of diazepam was reversed by L-arginine, a substrate for NO formation, but not by D-arginine. Methylene blue, the guanylate cyclase inhibitor, increased the protective efficacy of diazepam and clonazepam in the pentetrazole-induced seizures. 7-NI was able to potentiate the protective efficacy of diazepam and clonazepam in electroshock-induced tonic hindlimb extension. These findings suggest that the cGMP/NO system may participate in antiepileptic effects of benzodiazepines.
在小鼠戊四氮和电休克诱导的癫痫模型中，研究了一氧化氮（NO）对地西泮和氯硝西泮抗惊厥活性的影响。盐酸NG-硝基-L-精氨酸甲酯（L-NAME）显著提高了地西泮阈值剂量对戊四氮诱导的阵挛性和强直性惊厥及死亡的保护效果，而7-硝基吲唑（7-NI）的效果稍差。L-NAME对地西泮抗癫痫活性的上述增强作用被L-精氨酸（NO形成的底物）逆转，但未被D-精氨酸逆转。鸟苷酸环化酶抑制剂亚甲蓝提高了地西泮和氯硝西泮对戊四氮诱导癫痫的保护效果。7-NI能够增强地西泮和氯硝西泮对电休克诱导的强直性后肢伸展的保护效果。这些发现表明，cGMP/NO系统可能参与苯二氮䓬类药物的抗癫痫作用。
