The interaction of sildenafil with the anticonvulsant effect of diazepam

Taha Gholipour, Aylar Rasouli, Atieh Jabbarzadeh, Behtash Ghazi Nezami, Kiarash Riazi, Mohammad Sharifzadeh, Ahmad Reza Dehpour*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)79-83
Number of pages5
JournalEuropean Journal of Pharmacology
Volume617
Issue number1-3
DOIs
StatePublished - Sep 1 2009

Keywords

  • Benzodiazepine
  • Clonic seizure threshold
  • Nitric oxide/cyclic GMP signaling pathway
  • Pentylenetetrazole
  • Phosphodiesterase type-5 inhibitor

ASJC Scopus subject areas

  • Pharmacology

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