Effect of non-steroidal anti-inflammatory drugs on behavioral actions of diazepam in mice

Objectives: To investigate the behavioral pharmacological interactions of diazepam with nonsteroidal anti-inflammatory drugs.Methods: Non selective cyclooxygenase enzymeinhibitors (100 mg/kg acetylsalicylic acid, 10 mg/kgindomethacin, and 10 mg/kg diclofenac), a selective cyclooxygnase-1 inhibitor (10 mg/kg acetylsalicylicacid), and a selective cyclooxygnase-2 inhibitor (10mg/kg celecoxib) of non steroidal anti-inflammatory drugs were individually pretreated to 15 and 24 groups of Albino mice for dose and time dependent models (n=8, each treatment) before sleeping inducedby diazepam (20 mg/kg, intraperitoneally). In 6groups using an open field and 4 groups using traction test models (n = 10), 5 and 10 mg/kg of diazepam,intraperitoneally were given to induce sedation and muscle relaxation, and 2 mg/kg to induce anxiolyticaction after treatment with acetylsalicylic acid (10mg/kg) to 4 groups (n = 6). This study was carried out at the Al-Fateh Medical Science University, Tripoli,Libya between February and May 2009.Results: In dose and time dependent models nonselective cyclooxygenase and selective cyclo-oxygnase-1 inhibitors significantly reduced the duration of sleep induced by diazepam in mice by 60-75%, while the selective cyclooxygnase-2 inhibitor did not (p 0.05).However, anxiolytic, muscle relaxant, and sedativeeffects of diazepam were unchanged by acetylsalicylicacid.Conclusion: Non-steroidal anti-inflammatory drugs,most likely cyclooxygenase selective-1 inhibitors reduced the duration of sleep induced by diazepam,and this interaction could be of a pharmacodynamic type.