Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Taguchi, R. et al.

Nitric oxide-mediated effect of nipradilol, an alpha- and beta-adrenergic blocker, on glutamate neurotoxicity in rat cortical cultures.

Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy-3-nitroxy-2H-1-benzopyran) is used clinically as an anti-glaucoma ophthalmic solution in Japan, and was recently reported to suppress N-methyl-d-aspartate-induced retinal damage in rats. Here we investigated cytotoxic and cytoprotective actions of nipradilol on primary cultures of rat cortical neurons. Treatment of cortical cultures with a high concentration (500 microM) of nipradilol significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and nitrite concentration in culture medium, whereas desnitro-nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy-3-hydroxy-2H-1-benzopyran) had no significant effects. Nipradilol-induced neuronal damage was inhibited by S-hexylglutathione, a glutathione S-transferase inhibitor, and FeTPPS (5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride), a peroxynitrite decomposition catalyst. On the other hand, relatively low concentrations (10-100 microM) of nipradilol but not desnitro-nipradilol prevented neuronal cell death induced by 24 h application of 100 microM glutamate. Importantly, neuroprotective concentration (100 microM) of nipradilol suppressed glutamate-induced elevation of intracellular Ca2+ concentrations, but had no effect on intracellular cyclic GMP levels. Hence, nipradilol can protect cultured cortical neurons against glutamate neurotoxicity via cyclic GMP-independent mechanisms, and nitric oxide (NO) released from the nitoroxy moiety of nipradilol may mediate neuroprotective effect through the modulation of NMDA receptor function.[1]

References

Nitric oxide-mediated effect of nipradilol, an alpha- and beta-adrenergic blocker, on glutamate neurotoxicity in rat cortical cultures. Taguchi, R., Shirakawa, H., Yamaguchi, T., Kume, T., Katsuki, H., Akaike, A. Eur. J. Pharmacol. (2006) [Pubmed]

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