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The effect of synergistic interaction of levetiracetam and celecoxib on pentylenetetrazole- induced clonic and tonic seizures
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Azhdar Heydari   , Hassan Jamali , Marzieh Bazmandegan |
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Abstract: (265 Views) |
Introduction: Levetiracetam is a drug with anti-seizure, anti-inflammatory, and neuroprotective effects. Recent studies suggest that levetiracetam modulates brain inflammation pathways by inhibiting cyclooxygenase-2 enzyme. Therefore, the aim of this study was to investigate the synergistic interaction of levetiracetam and celecoxib (a cyclooxygenase-2 inhibitor) on the threshold for seizures induced by pentylenetetrazole (PTZ).
Methods and Materials: Eighty male NMRI mice weighing 25-30 g were divided into control and experimental groups receiving different doses of levetiracetam (50, 100, and 200 mg/kg), celecoxib (2.5, 5, and 10 mg/kg), or a combination of ineffective doses of levetiracetam and celecoxib. Levetiracetam and celecoxib were administered 45 and 30 minutes before the seizure test, respectively. Intravenous infusion of PTZ was used to induce seizures, and the onset time of myoclonic jerk, generalized clonus, and tonic hind limb extension were recorded and converted to seizure threshold dose.
Results: Levetiracetam at doses of 100 and 200 mg/kg and celecoxib at a dose of 10 mg/kg significantly reduced the threshold for clonic and tonic seizures. The combination of ineffective doses of levetiracetam (50 mg/kg) and celecoxib (5 mg/kg) significantly increased the threshold for clonic and tonic seizures induced by PTZ.
Conclusion: The anticonvulsant effect of the combination of ineffective doses of levetiracetam with celecoxib suggests that part of the effects of levetiracetam may be mediated centrally through inhibition of cyclooxygenase-2, although the exact mechanism of this potentiation needs further investigation.
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| Keywords: Levetiracetam, Cyclooxygenase-2, Celecoxib, Seizure |
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Full-Text [PDF 258 kb]
(42 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/17 | Accepted: 2023/08/23 | Published: 2023/08/23
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