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 properties 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 was assessed using in vivo magnetic resonance imaging. The rank order of potency for the NMDA antagonists tested was MK 801 > CGP 40116 approximately D-CPPene > CGS 19755. CGP 40116 dose-dependently reduced the volume of cortical infarction, with an ED50 of 11 mg/kg i.v., and its cerebroprotective efficacy was comparable to that of MK 801. Neuroprotection by CGP 40116 was still apparent when treatment was started 30 minutes after MCA occlusion. It is concluded that CGP 40116 is an effective cerebroprotectant with potential clinical utility for amelioration of focal cerebral ischemic damage.
Sauer
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Biology Research Laboratories, Ciba-Geigy Ltd., Basle, Switzerland.
Allegrini
P R
PR
Fagg
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GE
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018696:Neuroprotective Agents; D010875:Pipecolic Acids; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; C053672:selfotel; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate