Non-competitive NMDA antagonists, FR115427 and MK801, enhance neuronal survival in primary culture.
Primary culture of cerebral cortical neurons from mouse embryo was treated with non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, FR115427 and MK801. Both FR115427 and MK801 at 1-10 microM promoted neuronal survival after 7 days cultivation, determined by calorimetric assay for acid phosphatase (AP) activity. FR115426, the (-) isomer of FR115427 also promoted neuronal survival. However, competitive NMDA antagonists, APH and CGS19755 did not show promotive effect on neuronal survival at up to 100 microM. Anti-NMDA activity of these compounds was evaluated using an NMDA-induced convulsion assay. The relative potency of anti-NMDA activity was CGS19755 > MK801 > APH > FR115427 > FR115426. These data suggest that the effects on neuronal survival by FR115427 and MK801 are independent of anti-NMDA activity.
Ueda
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Katsuta
K
K
Nakanishi
H
H
Yoshida
K
K
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D051379:Mice; D009474:Neurons; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D016194:Receptors, N-Methyl-D-Aspartate; D044005:Tetrahydroisoquinolines; D016222:Fibroblast Growth Factor 2; C084456:1-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline; D016291:Dizocilpine Maleate