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

OBJECTIVE: To investigate the behavioral pharmacological interactions of diazepam with non steroidal anti-inflammatory drugs.

METHODS: Non selective cyclooxygenase enzyme inhibitors (100 mg/kg acetylsalicylic acid, 10 mg/kg indomethacin, and 10 mg/kg diclofenac), a selective cyclooxygnase-1 inhibitor (10 mg/kg acetylsalicylic acid), and a selective cyclooxygnase-2 inhibitor (10 mg/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 induced by diazepam (20 mg/kg, intraperitoneally). In 6 groups 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 anxiolytic action after treatment with acetylsalicylic acid (10 mg/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 non selective 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 sedative effects of diazepam were unchanged by acetylsalicylic acid.

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.