GYKI 52466 inhibits AMPA/kainate and peripheral mechanical sensory activity

The selectivity of the 2,3-benzodiazepine compound, GYKI 52466, was tested on wide dynamic range (WDR) dorsal horn neurons of the rat spinal cord. Using extracellular recordings, neurons were characterized by stimulation with noxious and innocuous intensities of the receptive field. In most cells, responses to iontophoretically applied (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or kainic acid (KA), but not N-methyl-D-aspartate (NMDA), were profoundly reduced by iontophoretic ejection of GYKI 52466. The inhibition usually lasted for 5-30 min following application of GYKI 52466. In a few neurons, responses to NMDA were also decreased by GYKI 52466. Responses to both noxious and innocuous mechanical stimulation were reduced in the presence of GYKI 52466. The results provide evidence for the selective inhibition by GYKI 52466 of AMPA/KA receptor-mediated functions and support the involvement of these receptors in spinal mechanical nociception.