DELAYED TREATMENT WITH A NONCOMPETITIVE NMDA ANTAGONIST, CNS-1102, REDUCES INFARCT SIZE IN RATS

The cerebroprotective effects of noncompetitive N-methyl-D-aspartate (NMDA) antagonists are well documented in animal focal ischemia models when the agents are administered prior to or just after ischemia begins. However, studies on the delayed administration of these drugs beyond the very acute stage of infarction are few and the results have varied. We assessed the extent of infarction and neurological outcome in 28 rats treated with either CNS-1102 (n = 14), a noncompetitive NMDA antagonist, or saline vehicle (n = 14), 1 h after ischemic onset using an intraluminal occlusion model of stroke. CNS-1102 significantly reduced lesion volume as assessed by 2,3,5-triphenyltetrazolium chloride staining at 24 h compared to saline-treated rats (120 +/- 30 vs. 251 +/- 20 mm(3), mean +/- SEM; p<0.001). The neurological outcome at 24 h was also significantly better in the CNS-1102 treated animals (p<0.04). The extent of the infarction was correlated with neurological outcome (p<0.01); larger lesions were associated with a poorer outcome. The results indicate that the time window for treatment with CNS-1102 is at least 1 h in this rat stroke model. The potential clinical efficacy of this compound is apparent but utility will depend, in part, on its side effect profile.