دراسة فارماكولوجية لتأثير مثبطات الالتهاب غير الستيرويدية على التأثير المضاد للتشنجات لعقار الديازبم في الفئران
Abstract Benzodiazepines are frequently prescribed as anxiolytics, sedatives hypnotics, and muscle relaxants as well as anticonvulsants. Non-steroidal anti-inflammatory drugs (NSAIDs) are also the most widely used for their anti-inflammatory, analgesic and antipyretic activities. Because of the chronic nature of epilepsy, NSAIDs may be used with benzodiazepines in patients with epilepsy. Therefore, there’s a probability of an interaction of NSAIDs and benzodiazepines in clinical practice. In order to study such interactions experimentally, an animal model was used. Thus, this thesis was aimed to explore pharmacological interactions between selective and non selective NSAIDs and diazepam anticonvulsant effect. Convulsion was induced in male albino mice by picrotoxin in two different doses (6 and 8 mg/kg), NSAIDs were used according to selectivity to cyclooxygenase enzyme (COX): Aspirin at 10 mg/kg (COX-1 selective inhibitor) and Aspirin at 100 and 200 mg/kg, diclofenac 10 and 20 mg/kg (non selective COX inhibitors) and celecoxib 20 mg/kg (COX-2 selective inhibitor). Diazepam at 1 and 2 mg/kg were chosen as low doses and parameters of convulsive behavior of picrotoxin deviation. psy, NSAIDs may be used with benzodiazepines in patients with epilepsy. Therefore, there’s a probability of an interaction of NSAIDs and benzodiazepines in clinical practice. In order to study such interactions experimentally, an animal model was used. Thus, this thesis was aimed to explore pharmacological interactions between selective and non selective NSAIDs and diazepam anticonvulsant effect. Convulsion was induced in male albino mice by picrotoxin in two different doses (6 and 8 mg/kg), NSAIDs were used according to selectivity to cyclooxygenase enzyme (COX): Aspirin at 10 mg/kg (COX-1 selective inhibitor) and Aspirin at 100 and 200 mg/kg, diclofenac 10 and 20 mg/kg (non selective COX inhibitors) and celecoxib 20 mg/kg (COX-2 selective inhibitor). Diazepam at 1 and 2 mg/kg were chosen as low doses and parameters of convulsive behavior of picrotoxin were observed in this thesis: onset time, episode frequency and death occurrence within post-injection of picrotoxin for 24 hrs. Aspirin in low dose (10 mg/kg) showed protection against death to about 50%. This protection which seems to be partially effective as anticonvulsant agent, however, higher dose of Aspirin (100 mg/kg) did not produce any significant change against convulsing in mice, Aspirin 200 mg/kg showed highly significant reduction of episode frequency (P < 0.001) and decreased percent of death. Furthermore, Aspirin 200 mg/kg in combination with diazepam has potentiated the effect of diazepam to complete protection against convulsion induced by picrotoxin. With respect to diclofenac, diclofenac pretreated-mice did not show any significant effect at 10 and 20 mg/kg with picrotoxin but in combination with diazepam showed significant potentiated effect of diazepam. Moreover, COX-2 inhibitor (celecoxib) alone delayed onset of convulsion without significant influence against the control but significantly decreased episodes and percent of death. Also in combination of celecoxib and diazepam, a highly potentiation of the effect and almost complete protection against convulsion behavior were noted (P < 0.001). Thus, it can be concluded that the studied NSAIDs have anticonvulsant behavior-like activity alone and in combination with diazepam. The most profound effect of anticonvulsant activity was showed in low episodes and mortality rate. In combination with diazepam, NSAIDs have more positive potential role in diazepam anticonvulsant effect. The present findings may also suggest that NSAIDs most likely COX-2 selective inhibitor is more potentiated diazepam’s anticonvulsant activity than COX-1 selective and non-selective inhibitors and such interaction could be more likely to be pharmacodynmic type.
نجمية محمد الزواوي (2014)
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