Document Type : Original Article
Authors
1
Assistant lecturer, clinical pharmacology department, faculty of medicine, zagazig university
2
Assistant professor of clinical pharmacology, clinical pharmacology Department, Zagazig University, Zagazig, Egypt, E mail :
3
clinical pharmacology department ,faculty of medicine, zagazig university
Abstract
Background: Ivabradine, Hyperpolarization activated cyclic nucleotide gated (HCN) channel blocker, is the most specific blocker of central nervous system Ih current. Valporate is one of the most commonly used antiepileptic drugs.
Objectives: investigate the possible anticonvulsant effect of Ivabradine and its interaction with valporate in pentylenetetrazole (PTZ) induced- kindling in mice.
Materials& Methods: mice were divided into four groups, “Group 1", "vehicle-treated group"
“Group 2", "PTZ kindling Control group "Group 3: Ivabradine ", group 4 Valproate (VPA) group 5" Ivabradine and VPA. Kindling was produced by repeated intraperitoneally (i.p). administration of PTZ (40mg/kg), every other day for 9 doses. Both drugs were administered i.p., 30 minutes before each PTZ injection. Seizure score, latency were recorded. Their brains were removed for assessment of oxidant/antioxidant status and anti-inflammatory cascades.
Results: Ivabradine and VPA individually significantly decreased seizure score and co administration of both drugs significantly decreased seizure score less than either vaporate or Ivabradine. Both drugs significantly increased latency to seizures.
Ivabradine, VPA and their combined administration significantly elevated brain level of GSH, catalase and significantly decreased levels of nitrite, MDA, IL1β, and TNFα as compared to PTZ control group. Co-administration of both drugs resulted in a significant elevation in the brain level of GSH, catalase concomitant with a significant reduction in the brain levels of MDA, IL1β and TNFα as compared to either VPA or ivabradine groups.
Conclusion: Ivabradine has anticonvulsant effect and potentiates the effect of VPA which may be attributes to HCN channel blockade, antioxidant and anti-inflammatory effects.
Keywords
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