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- W2018940596 abstract "In order to assess the role of nitric oxide/cyclicGMP signaling pathway in the anticonvulsant effect of benzodiazepines, we studied the potential interaction of a phosphodiesterase type 5 inhibitor, sildenafil with the effect of diazepam on a mouse model of clonic seizures induced by intravenous infusion of GABA antagonist, pentylenetetrazole (PTZ). Administration of sildenafil (10 mg/kg; per se effective on seizure threshold) could abolish the anticonvulsive effect of diazepam, and a subeffective dose (5 mg/kg), when added to NO precursor l-arginine (50 mg/kg) could cause the same effect. Conversely, subeffective doses of diazepam (0.02 mg/kg) and NO synthase inhibitor N(omega)-nitro-l-arginine methyl ester (L-NAME, 5 mg/kg), administered together, reversed the proconvulsive effect of sildenafil. Our findings indicate that the enhancement of NO/cGMP signaling pathway by sildenafil attenuates the anticonvulsant effect of the benzodiazepine prototype, diazepam. This suggests that the effects of facilitating GABAA-mediated inhibition and modulating NO pathways are additive and there might be a role for NO pathway in benzodiazepine effect against PTZ-induced seizures in mice." @default.
- W2018940596 created "2016-06-24" @default.
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- W2018940596 date "2009-09-01" @default.
- W2018940596 modified "2023-09-27" @default.
- W2018940596 title "The interaction of sildenafil with the anticonvulsant effect of diazepam" @default.
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- W2018940596 doi "https://doi.org/10.1016/j.ejphar.2009.06.061" @default.
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