Mebudipine and dibudipine protect PC12 cells against oxygen–glucose deprivation and glutamate-induced cell death

The protective effect of two new L-type calcium-channel blockers, mebudipine and dibudipine on neurotoxic effects induced by glutamate and oxygen–glucose deprivation (OGD) in PC12 cells was investigated. PC12 cells were intoxicated with two different methods. First, the cells were incubated with glutamate (10 μM/L), glutamate and mebudipine (10 μM/L), dibudipine (10 μM/L) or nimodipine (10 μM/L), on three different treatment schedules (concurrently, pre-3 h and pre-24 h). In the second method PC12 cells were exposed to in vitro oxygen–glucose deprivation for 30 min and 60 min alone or with the drugs in the same time schedules described above. Cellular viability was assessed by MTT assay. Glutamate-induced cell death and OGD-induced cell injury were attenuated significantly by mebudipine, dibudipine in comparison with nimodipine in all three different treatment schedules. Application of MK801 (10 μM/L), an antagonist of NMDA glutamate receptors inhibited PC12 cell death in both methods. Our study suggests that mebudipine and dibudipine, like nimodipine, may have protective effects against glutamate and oxygen–glucose deprivation-induced neurotoxicity.