Controversial action of positive modulator of subtype 7 of metabotropic glutamate receptors AMN082 on cortical epileptic afterdischarges in immature rats

Abstract

Some age-dependent epilepsies of infancy and childhood cannot be sufficiently treated with contemporaneous antiepileptics, therefore search for new mechanisms and new drugs active in pediatric patients is necessary. Possible anticonvulsant action of AMN082 (N,N′-dibenzhydryl-ethane-1,2-diamine dihydrochloride), a positive allosteric modulator of metabotropic glutamate receptor subtype 7, was examined in a model of epileptic afterdischarges elicited in three age groups of immature rats (12, 18 and 25 days old) by electrical stimulation of sensorimotor cortex. AMN082 did not exhibit an anticonvulsant action against spike-and-wave type of afterdischarges generated in the thalamocortical system; on the contrary, moderate proconvulsant action was found in 12- and 18-day-old rats (more marked prolongation of afterdischarges with repeated stimulations). On the other hand, AMN082 significantly shortened the second type of afterdischarges reflecting spread of epileptic activity into limbic system frequently recorded in 25-day-old rats. These contradictory results mean that AMN082 will not be a broad-spectrum anticonvulsant but it might be useful as a seizure-specific antiepileptic drug.