Effects of commercial antiglaucoma drugs to glutamate-induced [Ca2+]i increase in cultured neuroblastoma cells

Over releasing of glutamate and cellular calcium influx always results in neuronal death. In the present study, we investigated various commercial antiglaucoma drugs including timolol (0.58 muM to 58 muM), betaxolol (1.62 muM to 162 muM), carteolol (6.8 muM to 680 muM), pilocarpine (4.08 muM to 408 muM), latanoprost (0.01 muM to 1.1 muM), dorzolamide (6.16 muM to 616 muM), brinzolamide (2.6 muM to 260 muM), brimonidine (0.68 muM to 68 muM), dipivefrin (0.28 muM to 28 muM) and preservative benzalkonium chloride on their effects to inhibit glutamate-induced intracellular free Ca2+ ([Ca2+](i)) increase in cultured N1E-115 neuroblastoma cells. These drugs were diluted from original concentrations to 1/100, 1/1000 and 1/10000. The [Ca2+](i) mobility was studied after loading with fura-2-AM and analyzed by spectrofluorometry. It was found that betaxolol, dipivefrin and brimonidine have remarkable effects not only to inhibit the glutamate-induced [Ca2+](i) increase but also to decrease the basal [Ca2+](i). In the case of other drugs, only high concentration of timolol (58 muM) exhibited significant effect to completely prevent glutamate-induced [Ca2+](i) increase. Moreover, benzalkonium chloride did not exhibit any inhibitive effect. These results indicate that betaxolol, dipivefrin and brimonidine may have neuroprotective effects to inhibit the glutamate-induced over Ca2+ influx damage.