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.