Protective effect of ifenprodil against glucose deprivation-induced damage in cultured rat hippocampal neurons.
When hippocampal cultures were deprived of glucose, massive release of lactate dehydrogenase (LDH), an indicator of neuronal death, occurred 24 hr following the onset of hypoglycemic insult via N-methyl-D-aspartate (NMDA)-type glutamate receptor activation. Ifenprodil (0.1 and 1 M) significantly inhibited LDH release, which was antagonized by polyamines. These results suggest that ifenprodil protects neurons from glucose deprivation by antagonizing the effects of glutamate via selective interaction with polyamine modulatory sites on the NMDA receptor complex. The observed phenomenon further indicate that ifenprodil might be used prophylactically against neuronal death induced by excitotoxic disorders.
Geng
M Y
MY
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Japan.
Saito
H
H
Nishiyama
N
N
D000818:Animals; D015317:Biogenic Polyamines / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D004336:Drug Antagonism; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D015317:Biogenic Polyamines; D003470:Culture Media; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D007770:L-Lactate Dehydrogenase; D005947:Glucose; C010739:ifenprodil