GYKI-52466 INHIBITS AMPA KAINATE AND PERIPHERAL MECHANICAL SENSORY ACTIVITY/

The selectivity of the 2,3-benzodiazepine compound, GYKI 52466, was te sted on wide dynamic range (WDR) dorsal horn neurons of the rat spinal cord. Using extracellular recordings, neurons were characterized by s timulation with noxious and innocuous intensities of the receptive fie ld. In most cells, responses to iontophoretically applied pha-amino-3- hydroxy-5-methylisoxazole-4-propionate (AMPA) or kainic acid (KA), but not N-methyl-D-aspartate (NMDA), were profoundly reduced by iontophor etic ejection of GYKI 52466. inhibition usually lasted for 5-30 min fo llowing application of GYKI 52466. In a few neurons, responses to NMDA were also decreased by GYKI 52466. Responses to both noxious and inno cuous mechanical stimulation were reduced in the presence of GYKI 5246 6. The results provide evidence for the selective inhibition by GYKI 5 2466 of AMPA/KA receptor-mediated functions and support the involvemen t of these receptors in spinal mechanical nociception.