Jpn. J. Pharmacol. 73 (1), 97-100 (1997)

Protective Effect of Ifenprodil against Glucose Deprivation-Induced Damage in Cultured Rat Hippocampal Neurons

Mei-Yu Geng, Hiroshi Saito and Nobuyoshi Nishiyama (*)

Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan
(*) To whom correspondence should be addressed.

Abstract: 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.

Keywords: Ifenprodil, Hippocampal cultured neuron, Excitotoxic disorder