GYKI 52466, an inhibitor of spinal reflexes is a potent quisqualate antagonist

Abstract

GYKI 52466 is a 2,3-benzodiazepine compound, which inhibits spinal reflexes in cats. Contrary to the classical benzodiazepines (e.g. diazepam), GYKI 52466 does not potentiate the inhibitory action of gamma-amino butyric acid, but seems to affect excitatory processes in the spinal cord directly.

We have investigated the effect of GYKI 52466 on excitatory transmission and on the effect evoked by iontophoretic application of various excitatory amino acids in rat somatosensory cortex slices.

The neuronal depolarizations caused by iontophoretic application of glutamate, quisqualate and kainate were dose dependently depressed by adding 10—50 μM GYKI 52466 to the perfusing medium, whereas Af-methyl-D-aspartic acid (NMDA) responses were unaffected. Further, the excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the corpus callosum were inhibited by both perfusion- and iontophoretic application of GYKI 52466.

The maximum depression of the EPSPs was by about 80%. Quisqualate responses were similarly reduced, whereas glutamate responses were less affected.

In conclusion, GYKI 52466 appears to be a selective blocker of excitatory responses mediated by non-NMDA receptors. Our results also indicate that these receptors play a substantial role in the generation of postsynaptic potentials in the somatosensory cortex.