THE NEUROPROTECTIVE EFFECT OF THE FOREBRAIN-SELECTIVE NMDA ANTAGONISTCP101,606 UPON FOCAL ISCHEMIC BRAIN-DAMAGE CAUSED BY ACUTE SUBDURAL-HEMATOMA IN THE RAT

The neuroprotective effects of drugs that act against excitotoxic dama ge, caused by glutamate, are well described in focal ischemia, but beh avioral effects, and apparent failure in clinical trials of ''first-ge neration'' competitive N-methyl D-aspartate (NMDA) antagonists, such a s Selfotel (CGS19755), has led to interest in evaluating newer NMDA an tagonists,vith fewer behavioral effects, We have therefore evaluated t he neuroprotective effect of a new forebrain-selective polyamine site NMDA antagonist, CP101,606 in a rat subdural hematoma (SDH) model, An SDH was produced by slow injection of 0.4 ml autologous blood into the parietal subdural space, Brain damage was assessed histologically at eight coronal planes, in animals sacrificed 4 h after induction of hem atoma, The drug was infused 30 min after induction of SDH. The reducti ons of ischemic brain damage achieved by CP101,606, was 29% for the lo w dose and 37% for the high dose, This novel glutamate antagonist has shown a magnitude of neuroprotection which is comparable with that see n with ''first-generation'' NMDA antagonists such as MK801, D-CPP-ene and CGS19755, in this same model, This new agent is claimed to have fe wer psychomotor and behavioral effects than MK801, D-CPP-ene, and CGS1 9755.