PROTECTION FROM HIGH-PRESSURE INDUCED HYPEREXCITABILITY BY THE AMPA KAINATE RECEPTOR ANTAGONISTS GYKI-52466 AND LY-293558

The neurophysiological effects of 2 novel AMPA/kainate receptor antago nists, GYKI 52466 and LY 293558, on the high pressure neurological syn drome have been investigated in the rat and baboon (GYKI 52466) and ra t (LY 293558). Rats were exposed to increasing ambient pressures of he lium and oxygen at 3 ATA/min, on one occasion each. GYKI 52466 at 20 m u mol/kg i.v. immediately before, followed by 70 mu mol/kg/hr i.v. dur ing compression delayed tremor by 85% and myoclonus by 30%, compared w ith control vehicle, and no side effects were observed. Seizure activi ty was not affected by any of the doses used. LY 293558 at 36 mu mol/k g i.p. delayed tremor and myoclonus (44% and 12%), LY 293558 72 mu mol /kg additionally delayed seizure activity (21%). Side effects, princip ally tranquillization at the higher dose, were also noted.