Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurons against glutamate-induced damage.
A disturbed cellular calcium homeostasis is suggested to play a pivotal role in neuronal damage. Energy deficiency causes depolarization of the neuronal membrane and Ca2+ enters the cells through different ion channels, the voltage-sensitive L-type Ca2+ channels and the NMDA-operated channels being the main gates. In the present study we used primary cultures of rat hippocampal neurons to demonstrate that the dihydropyridine calcium antagonist nimodipine, the non-competitive NMDA antagonists dizocilpine and memantine, as well as the AMPA antagonist NBQX (2,3-dihydroxy-6-nitro -7-sulfamoyl-benzo(F)quinoxaline), attenuate the glutamate-induced neuronal damage dose-dependently. Nimodipine applied simultaneously with NMDA-antagonists and NBQX, respectively, resulted in somewhat greater neuroprotection of glutamate-treated neurons compared with the effects of these agents applied singly. The type of interaction is best described by an independent action in combination, which means that the relative effects of nimodipine were not enhanced. Therefore, it can be considered as a lack of potentiation.
Krieglstein
J
J
Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie und Lebensmittelchemie, Philipps-Universitât, Marburg, Germany.
Lippert
K
K
Pöch
G
G
D000818:Animals; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology; D008559:Memantine / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins; D009553:Nimodipine / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D009553:Nimodipine; D016291:Dizocilpine Maleate; D008559:Memantine