Objectives: The anticonvulsant and antioxidant effects of lamotrigine on status epilepticus (SE) are incompletely understood. We assessed these effects of lamotrigine on pilocarpine (Pilo)-induced SE in mice.
Methods: Male C57BL/J6 mice were assigned to three groups: the control group, Pilo (400 mg/kg, s.c.)-induced SE (Pilo group) and lamotrigine (20 mg/kg, i.p.) treated (Pilo/lamotrigine group). The latency to SE of Racine's stage 3 or higher, the mortality rate within 2 h of Pilo administration, and the duration of SE until sacrifice were examined. Nitric oxide (NO), malondialdehyde and glutathione of oxidative stress biomarkers were detected in the hippocampus of the sacrificed animals in the above groups. NO was also detected in the cultured rat hippocampal neurons treated with 4 μM Pilo, Pilo+100 μM lamotrigine (Pilo/lamotrigine) and Pilo/lamotrigine+ N-methyl-D-aspartic acid (NMDA) receptor antagonist (10 μM MK-801, 3 μM ifenprodil) to examine the antioxidant effects of lamotrigine via non-NMDA-related pathways.
Results: lamotrigine prolonged the latency to SE, the SE duration until sacrifice, and decreased the mortality rate in mice with Pilo-induced SE. Lamotrigine also decreased hippocampal concentrations of NO and malondialdehyde and increased the concentrations of glutathione in the SE model. Furthermore, there were significant differences in NO concentrations between groups of cultured rat hippocampal neurons treated with Pilo and Pilo/lamotrigine, and with Pilo/lamotrigine and Pilo/lamotrigine+MK-801.
Conclusion: Our findings suggest that lamotrigine exerts anticonvulsant and antioxidant effects on SE, but its antioxidant activity may not be fully exerted via NMDA-related pathways.
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