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

European Journal of Pharmacology
Ryota TaguchiAkinori Akaike

Abstract

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...Continue Reading

References

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Aug 21, 2002·Current Eye Research·Toru NakazawaMakoto Tamai
Mar 27, 2003·Investigative Ophthalmology & Visual Science·Kazue TakahataAkinori Akaike
Oct 3, 2003·European Journal of Pharmacology·Ryota TaguchiAkinori Akaike

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Citations

May 20, 2017·Neurochemical Research·Yoshiki Koriyama, Ayako Furukawa
Jul 17, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Holly D Bauser-Heaton, H Glenn Bohlen
Feb 13, 2007·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shyam S SharmaRavinder K Kaundal

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