Effects of Commercial Antiglaucoma Drugs to Glutamate-Induced [Ca 2+ ] i Increase in Cultured Neuroblastoma Cells

Abstract

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 μM to 58 μM), betaxolol (1.62 μM to 162 μM), carteolol (6.8 μM to 680 μM), pilocarpine (4.08 μM to 408 μM), latanoprost (0.01 μM to 1.1 μM), dorzolamide (6.16 μM to 616 μM), brinzolamide (2.6 μM to 260 μM), brimonidine (0.68 μM to 68 μM), dipivefrin (0.28 μM to 28 μM) 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 μM) 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.