Effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid on focal cerebral ischemia in cat.
The effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was examined in a cat model of focal cerebral ischemia. Effect of CGP 40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intravenously 30 min before left middle cerebral artery (MCA) occlusion. After MCA occlusion for 8 h, infarction spreaded widely among caudate nucleus prepyriform cortex, amygdala and temporal lobe cortex in the ischemic hemisphere. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly decreased the infarcted area. CGP 40116 was effective in the frontal and central brain, although CGS 19755 showed neuroprotective effect in almost all sites. Thus, the compounds are potent neuroprotectants in focal ischemia.
Okada
M
M
Drug Discovery Research Unit, Ciba-Geigy Japan Limited, Takarazuka, Japan.
Ueda
H
H
Kometani
M
M
Nakao
K
K
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D002415:Cats; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; C053672:selfotel; D015763:2-Amino-5-phosphonovalerate