Neuroprotective effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid in the gerbil model of transient global cerebral ischemia.
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 mongolian gerbil model of global 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 intraperitoneally 30 min before bilateral carotid artery occlusion. At 4 days after the ischemia, locomotor activity was significantly higher in ischemic control mongolian gerbils in comparison with sham-operated mongolian gerbils. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly suppressed the increase of the motility. Seven days after ischemia, ischemic control group was still hyperactive compared to sham-operated group. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly reversed it. The number of survived neurons of ischemic control group was significantly less than that of sham-operated group at 7 days after ischemia. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly increased the number of survived neurons. It is concluded that CGP 40116 is more potent for amelioration of global cerebral ischemic damage than CGS 19755.
Okada
M
M
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Ueda
H
H
Kometani
M
M
Nakao
K
K
Kohjimoto
Y
Y
Takahashi
I
I
Tanaka
I
I
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; 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