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Pharmacologia

Year: 2014 | Volume: 5 | Issue: 9 | Page No.: 351-356
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Authors

Jana Tchekalarova

R.M. Freitas

Keywords

Research Article

Effect of Diterpene Phytol on Pentlylenetetrazol and Maximal Electroshock Seizure Models: Possible Role of GABAergic Mechanism

Jana Tchekalarova and R.M. Freitas
Background: Recently, diterpene phytol was characterized as a potent anticonvulsant in a pilocarpine model. The present study explores the efficacy of phytol in pentylenetetrazol (PTZ) and the Maximal Electroshock Seizure (MES) models and the possible role of GABAergic mechanism. Materials and Method: Mice were pretreated with phytol (50, 75, 200 and 250 mg kg-1, i.p.) 30 min before the convulsant or corneal electroshock, respectively. Diazepam (2, 5 mg kg-1, i.p.) and flumazenil (25 mg kg-1, i.p.) were used as reference drugs. Motor coordination was evaluated by rotarod test. Results: Phytol dose-dependently increased the latency of onset of clonic and tonic-clonic seizures in the PTZ model. However, unlike diazepam, it failed to decrease the incidence of clonic seizures. The highest dose of phytol protected the animals against the incidence of tonic-clonic seizures and death while the antagonist of benzodiazepine receptors blocked the anticonvulsant effect of this diterpene. Furthermore, although not as efficient as diazepam, the highest dose of phytol prevented the tonic extension and showed a tendency to alleviate the mortality in MES test. Flumazenil failed to block the anticonvulsant effect of phytol in the MES test. Motor impairment, evaluated with the rotarod test, was minimal at the highest dose of phytol. Conclusion: The results suggest that although the hightest dose of 250 mg kg-1 phytol suppressed the seizure activity it appeared less potent than diazepam in both the PTZ and MES test. The possible GABAergic mechanism involved in the diterpene activity is discussed.
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