Effects of Non-Steroidal Anti-Inflammatory Drugs on Anticonvulsant Activity of Diazepam in Mice

Abstract

As a result of the chronic nature of epilepsy, patients often need concurrent therapy for other diseases. The benzodiazepines are frequently prescribed as anxiolytics, sedatives and hypnotics and these agents may interact with other drugs. Non- steroidal anti-inflammatory drugs (NSAIDs) are commonly used as anti-inflammatory, analgesic and antipyretic agents. They prescribed and used with diazepam in many clinical cases. In this study, convulsions were chemically induced in Albino mice by given picrotoxin (6 mg/kg). The animals were divided into several groups as following: picrotoxin, diazepam (1 mg/kg), aspirin (10, 100 & 200 mg/kg), diclofenac (10 & 20 mg/kg) and Celecoxib 20 mg/kg. All drugs were given intra peritoneally 30 minute before picrotoxin intake. In combination treatment, the NSAIDs were administrated 30 minute before diazepam; the latter was given 30 minute before picrotoxin. The following parameters were recorded: onset time in minutes, number of seizures (attacks) in each group and death occurrence within 24 hours after treatments. Administration of NSAIDs with diazepam showed that aspirin 200 mg/kg, diclofenac (in both doses) and celecoxib potentiated the effect of diazepam (p ≤ 0.001) while aspirin 10 mg/kg showed no effect on diazepam but aspirin 100 mg/kg reduced the anticonvulsant's effect of diazepam (p ≤ 0.05). Thus, these findings may suggest that acute use of NSAIDs, of selective COX-2 inhibitors, but not nonselective COX inhibitors potentiate the effect of diazepam's anticonvulsant effect and this interaction could be of pharmacodynamic type.