Issn Print: 0265-0215

Publication Date: 2007/06/01


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Protective effect of nefopam on seizure activity in mice: 9AP4-4

M. Czuczwar; K. Czuczwar; J. Kis; A. Kolacz; K. Przesmycki

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Background and Goal of Study: Nefopam is a centrally acting non-opioid analgesic with not completely understood mechanism of action. Adverse effects associated with therapeutic use and overdose of nefopam are mainly associated with central nervous system and include hallucinations, cerebral oedema and convulsions. To the best of our knowledge, no research was conducted on influence of nefopam on seizure activity nor possible interactions between nefopam and antiepileptic drugs. Therefore, the aim of this study was to assess the effect of nefopam administration on electrical threshold and its influence on protective activity of antiepileptic drugs in the maximal electroshock test in mice.
Materials and Methods: Experiments were performed on male Swiss mice, weighing 20-25g. The following antiepileptics were used: valproate, carbamazepine, phenobarbital, and phenytoine. The convulsive threshold was evaluated as CS50, which is the current strength (in mA), necessary to produce tonic hindlimb extension in 50% of the animals tested. In order to estimate the anticonvulsant ED50 values (50% effective anticonvulsant dose) of studied antiepileptics (given alone or in combination with nefopam) mice were pretreated with different doses of the drugs and then challenged with maximal electroshock (25 mA).
Results and Discussion: Nefopam significantly elevated the electric seizure threshold at the dose of 5 mg/kg, whilst the dose of 1 mg/kg had no effect on seizure activity. The protective activity of studied antiepileptics were significantly enhanced by co-administration of nefopam at the dose of 5mg/kg. Nefopam at the dose of 1 mg/kg had no effect on the protective activity of studied drugs.
Conclusion: Nefopam exerts anticonvulsive effect when given alone and potently enhances the protective activity of valproate, carbamazepine, phenobarbital, and phenytoine in the experimental seizure models in mice.
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