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 microM to 58 microM),
betaxolol (1.62 microM to 162 microM),
carteolol (6.8 microM to 680 microM),
pilocarpine (4.08 microM to 408 microM),
latanoprost (0.01 microM to 1.1 microM),
dorzolamide (6.16 microM to 616 microM),
brinzolamide (2.6 microM to 260 microM),
brimonidine (0.68 microM to 68 microM),
dipivefrin (0.28 microM to 28 microM) and preservative
benzalkonium chloride on their effects to inhibit
glutamate-induced intracellular free Ca(2+) ([Ca(2+)](i)) increase in cultured N1E-115
neuroblastoma cells. These drugs were diluted from original concentrations to 1/100, 1/1000 and 1/10000. The [Ca(2+)](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 [Ca(2+)](i) increase but also to decrease the basal [Ca(2+)](i). In the case of other drugs, only high concentration of
timolol (58 microM) exhibited significant effect to completely prevent
glutamate-induced [Ca(2+)](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 Ca(2+) influx damage.