HA-966 (1-hydroxy-3-aminopyrrolidone-2) selectively reduces N-methyl-D-aspartate (NMDA)-mediated brain damage.
The neuroprotective effects of the strychnine-insensitive glycine receptor antagonist, HA-966, against N-methyl-D-aspartate (NMDA)- and quisqualate (QA)-mediated brain injury were determined in perinatal rats. Postnatal day (PND) 7 rats received intrastriatal injections of NMDA (25 nmol) or QA (100 nmol) and then were administered intraperitoneal (i.p.) injections of varying doses of HA-966 or vehicle 15 min later. Animals were sacrificed 5 days later and the degree of brain injury was calculated by comparison of the weights of injected and contralateral cerebral hemispheres. HA-966 selectively reduced the degree of NMDA-mediated brain injury in a dose-dependent manner. However, HA-966 did not attenuate QA-mediated brain injury.
McDonald
J W
JW
Neuroscience and Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor.
Uckele
J
J
Silverstein
F S
FS
Johnston
M V
MV
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000008:administration & dosage / Q000494:pharmacology; D001927:Brain Diseases / Q000139:chemically induced* / Q000517:prevention & control; D003342:Corpus Striatum / Q000187:drug effects; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology; D011760:Pyrrolidinones / Q000627:therapeutic use*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D010069:Oxadiazoles; D011760:Pyrrolidinones; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; C001369:1-hydroxy-3-amino-2-pyrrolidone