Effect of KB-2796, a new diphenylpiperazine Ca2+ antagonist, on glutamate-induced neurotoxicity in rat hippocampal primary cell cultures.
The effects of the novel calcium channel antagonist KB-2796, other calcium channel antagonists, an N-methyl-D-aspartate (NMDA) antagonist, non-NMDA antagonists, Mg2+, a Ca(2+)-chelator and a calcium channel agonist on neurotoxicity induced by a 10-min application of 100 microM glutamate were studied in rat hippocampal primary cell cultures. KB-2796 (0.1 and 1 microM), flunarizine (1 microM), nimodipine (10 microM), MK-801 (0.01-1 microM), Mg2+ (10 mM) and EGTA (10 mM) significantly prevented the neurotoxicity, but 6-cyano-7-nitro-quinoxalinedione (CNQX) (10 microM) and 6, 7-dinitro-quinoxalinedione (DNQX) (10 microM) did not. Bay K 8644 (10 and 100 nM) enhanced the neurotoxicity. These findings indicate that KB-2796 protects the neuronal cell from the glutamate-induced neurotoxicity, presumably by blocking the Ca2+ influx into brain neurons.
Hara
H
H
Department of Pharmacology, Kanebo Ltd. Osaka, Japan.
Yokota
K
K
Shimazawa
M
M
Sukamoto
T
T
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D005971:Glutamates; D010879:Piperazines; D018698:Glutamic Acid; D016202:N-Methylaspartate; C052424:lomerizine