DOI: 10.5176/2345-783X_PHARMA15.60
Authors: R.Jayaraman, C.K.Ashok Kumar, S. Mohanalakshmi, S. Vijayaraj Sree Vidyanikethan
Abstract:
Objectives: The objective of this study was to screen the influence of atorvastatin on the anticonvulsant activity of lacosamide and levetiracetam by maximal electroshock-induced electro convulsions in mice. Methods: The maximal seizure pattern was induced in mice by giving an alternating current of 45 mA for 0.2 Sec. Atorvastatin (10mg/kg i.p) were administered intraperitoneally 30 min before the electrical induction of seizures in alone and in combination with lacosamide (10mg/kg i.p) and levetiracetam (10mg/kg i.p).The ability of atorvastatin either alone or in combination with antiepileptics to reduce/abolish the extensor phase of MES induced electro convulsions was considered as antiepileptic criteria. Additionally, the effects of atorvastatin on the adverse effect potential were assessed by chimney test for its motor performance whereas rota rod, elevated pluz maze and forced swim test were used to record the behavioral effects periodically. In order to estimate the pharmacokinetic interaction between antiepileptic drugs and atorvastatin, the plasma drug concentrations were estimated by HPLC method. Key findings: Results shown that, in atorvastatin plus levetiracetam group there was no significant reduction of tonic extension were observed but the concurrent administration of lacosamide with atorvastatin at a dose level of 10mg/kg reduces the potency of tonic extension (Day 1 & 3 -** P<0.01: Day 5 & 7 -*** P<0.001) throughout the acute study when compared with control groups. Moreover atorvastatin in combinations with both antiepileptic drugs had no impact on their adverse effects in the chimney test. Conclusions : Based on the study, the results suggest that the HMG-CoA reductase inhibitor atorvastatin significantly enhanced the anticonvulsant action of lacosamide possibly due to its pharmacokinetic interaction whereas there was no significant protection were observed in atorvastatin plus levetiracetam group which shows that atorvastatin plus levetiracetam fails to protect the seizures in MES convulsion model.
Keywords: Atorvastatin, Phenytoin, MES Convulsion, lacosamide, levetiracetam
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