Effect of CP101,606, a Novel NR2B Subunit Antagonist of the N -Methyl- d -Aspartate Receptor, on the Volume of Ischemic Brain Damage and Cytotoxic Brain Edema After Middle Cerebral Artery Occlusion in the Feline Brain

Abstract

CP101,606 ranks very highly among the current neuroprotection candidates for clinical trials, and its excellent safety record in both animals and phase II studies in conscious, moderate head injury patients suggests that it will be highly effective in human occlusive stroke.

Transient Down-regulation of NMDA Receptor Subunit Gene Expression in the Rat Retina Following NMDA-induced Neurotoxicity is Attenuated in the Presence of the Non-competitive NMDA Receptor Antagonist MK-801

“…These data, together with the results of the present study suggests that NMDA-induced toxicity is determined by the subunit composition of the NMDA receptor, speci®-cally by the inclusion of an NR2A and/or NR2B subunit. Although further studies are needed to address this question, evidence suggesting that the NR2A and/or the NR2B subunit participate in initiating neurotoxicity in other regions of the brain has been presented by others (Anegawa et al, 1995;Di et al, 1997;Menniti et al, 1997;Zhang et al, 1997;Morikawa et al, 1998). Morikawa et al (1998) hypothesize that the NR2A subunit plays a direct role in mediating neuronal cell death in the cerebral cortex following ischemia.…”

Deteriorating Stroke: Diagnostic Criteria, Predictors, Mechanisms and Treatment

“…The potential of glutamate to induce cell swelling is well known [42, 43]. The presence of early hypodensity on brain CT associated with progressing stroke [4, 8]probably represents intracellular edema.…”

Ion Channels as Drug Targets in Central Nervous System Disorders

“…In this field the NR2B-selective type of non-competitive antagonists has a strong potential, showing both analgesic and neuroprotective activity together with slight side effects [178,224]. Many NR1/NR2B antagonists, including ifenprodil, eliprodil and the selective and potent congeners, traxoprodil and Ro 25-6981, offer promise in preclinical models of ischemia [225][226][227][228][229].…”