Anticonvulsive effect of AMPA receptor antagonist GYKI 52466 on 4-aminopyridine-induced cortical ictal activity in rat

Abstract

The effect of GYKI-52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine), a selective antagonist of AMPA receptor was investigated on the generation and manifestation of 4-aminopyridine-induced cortical epileptiform activity. In vivo experiments were carried out on pentobarbital-anaesthetised adult rats. Ictal epileptiform activity was induced by local application of 4-aminopyridine (4-Ap) to the surface of somatosensory cortex. In one group of animals, GYKI 52466 was administered intraperitoneally before 4-Ap application, in another group, the already active primary focus was treated locally by GYKI 52466. Different parameters of epileptic activity were measured and compared in GYKI 52466-treated and control animals. The results demonstrate that GYKI 52466 exerts anticonvulsive effects on both the induction and the expression of epileptiform activity, by delaying the onset of the first ictal event, decreasing the numbers and duration of ictal periods, as well as the amplitudes of epileptiform discharges both in the primary and mirror foci. However, seizure propagation to other cortical areas seemed to be facilitated. The anticonvulsive effect of GYKI 52466 was stronger in pretreatment than in treatment of ongoing epileptiform activity. As a conclusion, it is supposed that AMPA receptors are probably more dominant in the induction of epileptiform activity than in the maintenance of it, mainly through the activation of cortico-thalamo-cortical networks. It is also supposed that the cortical inhibition which blocks the propagation of epileptiform process might be activated mainly through non-N-methyl-D-aspartate receptors.