Anti-ictogenic and antiepileptogenic properties of perampanel in mature and immature rats
Perampanel (PER) is a selective noncompetitive antagonist at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, the first of its class approved for the adjunctive treatment of partial onset seizures and generalized seizures. This study explored anti-ictogenic and antiepileptogenic effects of PER in rats at different stages of development.
Using a rapid kindling model in postnatal day 14 (P14), P21, P28, and P60 rats, we studied two doses of PER: 1 and 2 mg/kg injected intraperitoneally 30 min before afterdischarge assessment. We also assessed blood and brain concentrations of PER 30 min after the injection.
PER 2 mg/kg significantly increased the afterdischarge threshold (ADT) at all ages, whereas PER at 1 mg/kg increased ADT only in P21 rats. PER 2 mg/kg also shortened the afterdischarge duration in P14 and P28 rats. PER increased the number of stimulations required to achieve a stage 4–5 seizure in a dose-dependent manner in P14 and P21 rats, with almost complete elimination of stage 4–5 seizures. At P28, only PER 2 mg/kg increased the number of stimulations required to develop a stage 4–5 seizure. In contrast, PER had no effect on the number of stage 4–5 seizures at P60. We did not observed any age-dependent significant difference in the serum and brain levels of PER 30 min after the injection.
PER exerted anti-ictogenic effects from P14 to P60 independent of brain maturation. PER also exhibited antiepileptogenic effects with a stronger effect in the younger animals.