An antagonist of calcium permeable AMPA receptors, IEM1460: Anticonvulsant action in immature rats?

AMPA receptors lacking GluA2 subunit are widely distributed in developing brain. IEM1460 as a specific antagonist of these receptors might be a potential age-specific anticonvulsant. Possible anticonvulsant action was assessed in two models of epileptic seizures: pentylenetetrazol (PTZ) induced convulsions and cortical afterdischarges elicited in 12-, 18- and 25-day-old rats. IEM1460 was administered intraperitoneally in doses of 3, 10 and 20 mg/kg. Pretreatment with IEM1460 at the dose of 20 mg/kg resulted in delayed onset of PTZ-induced minimal clonic seizures in all age groups. PTZ-induced generalized tonic clonic seizures were suppressed in 18- and 25-day-old rats by 10 and 20 mg/kg doses of IEM1460. Duration of cortical afterdischarges progressively increased with repeated stimulations in control 12-day-old rats. The IEM1460 dose of 10 mg/kg fully blocked this prolongation and the 20-mg/kg dose partly suppressed it. Administration of IEM1460 had moderate proconvulsant effect on 18- and 25-day-old animals afterdischarges were prolonged with repeated stimulations. The duration of cortical epileptic afterdischarges in adult (80-day-old) animals was not affected by IEM1460. Effects of IEM1460 are dependent on the model of seizures used, their ictogenic structures and developmental changes in subunit composition of AMPA receptors. (C) 2014 Elsevier B.V. All rights reserved.