A new non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist, GYKI 52466, was tested on L-glutamate (Glu)-, kainate (KAI)- and NMDA-induced responses in vivo, using both extracellular recording of antidromic field potentials and intracellular recording from rat abducens motoneurones. Intravenous (5-10 mg/kg) or iontophoretic applications of GYKI 52466 blocked the Glu-induced depression of antidromic field potentials only. Furthermore, intravenous application of ketamine blocked the NMDA-induced depression only. Iontophoretic application of GYKI 52466 reduced the Glu-induced neuronal depolarization but not those induced by NMDA and KAI. Our results show a selective blockade of Glu responses by GYKI 52466, probably by acting at the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subtype in rat abducens motoneurones.