THE COMPETITIVE NMDA RECEPTOR ANTAGONIST CGP-40116 IS A POTENT NEUROPROTECTANT IN A RAT MODEL OF FOCAL CEREBRAL-ISCHEMIA

Focal cerebral ischemia was induced in rats by permanent occlusion of the left middle cerebral artery (MCA). The cerebroprotective propertie s of the competitive NMDA antagonist CGP 40116 were evaluated in that model and compared to the neuroprotective effects of MK 801, D-CPPene and CGS 19755 under the same experimental conditions. Infarct volume w as assessed using in vivo magnetic resonance imaging. The rank order o f potency for the NMDA antagonists tested was MK 801 > CGP 40116 simil ar to D-CPPene > CGS 19755. CGP 40116 dose-dependently reduced the vol ume of cortical infarction, with an ED(50) of 11 mg/kg i.v., and its c erebroprotective efficacy was comparable to that of MK 801. Neuroprote ction by CGP 40116 was still apparent when treatment was started 30 mi nutes after MCA occlusion. It is concluded that CGP 40116 is an effect ive cerebroprotectant with potential clinical utility for amelioration of focal cerebral ischemic damage.