The role of glutamate and GABA receptors in the anticonvulsive effects of levetiracetam and a 4-phenylpirrolidone derivative (GIZh-290) in rats

Abstract

The method of radioligand binding ex vivo has been used to evaluate the involvement of the ionotropic and metabotropic glutamate and GABA receptors in the mechanism of anticonvulsant action of levetiracetam and the original compound GIZh-290 (2-oxo-4-phenylpyrrolidin-1-yl) acetic acid) in the rat brain. We found that at the peak of lithium-pilocarpine seizures, the B_max value (the density of specific binding sites) decreases for [³H]-SR 95531, [³H](–)baclofen, [³Н](+)MK-801, and [³H]LY 354740 by 30–50% from the control level. The pre-treatment with levetiracetam (600 mg/kg) 40 minutes before pilocarpine kept the number of GABA- and NMDA-type receptors at the control level without affecting the metabotropic receptors. The administration of GIZh-290 (5.0 mg/kg), in contrast, maintained the density of GABA_A receptors at the control level, while the density of other types of receptors remained decreased at the peak of seizures. Thus, the anticonvulsant effect of levetiracetam and GIZh-290 has different mechanisms.