T-477, a novel Ca2+- and Na+ channel blocker, prevents veratridine-induced neuronal injury

Kayoko Okuyama, Satoko Kiuchi, Masahito Okamoto, Hiroshi Narita, Yukitsuka Kudo

    Research output: Contribution to journalArticlepeer-review

    18 Citations (Scopus)

    Abstract

    To evaluate the effect of (R)-(+)-2-(4-chlorophenyl)-2,3-dihydro-4-diethyl aminoacetyl-4H-1,4-benzothiazine hydrochloride (T-477), a novel Na+- and Ca2+ channel blocker, on neuronal injury in vitro, we studied veratridine-induced injury in cultured rat hippocampal neurons. Neurons swelled extensively 10 min after the addition of veratridine, and returned to their initial size within 2 h. Intracellular Na+ and Ca2+ concentrations and amino acid release from the cells, in particular, that of glutamate, increased after the treatment with veratridine. Approximately 70% of neurons died within 24 h. T-477 inhibited both veratridine-induced swelling and death in a concentration-dependent manner. Moreover, T-477 concentration dependently reduced the increases in Na+ and Ca2+ influx and amino acid release. These results suggest that T-477 prevented the veratridine-induced influx of Na+ and, thereby, reduced neuronal swelling. This, combined with the effects of T-477 on the inhibition of Ca2+ influx and glutamate release, possibly by the blockade of Na+ channels, may be the mechanism by which T-477 protects neurons from death induced by veratridine. Copyright (C) 2000 Elsevier Science B.V.

    Original languageEnglish
    Pages (from-to)209-216
    Number of pages8
    JournalEuropean Journal of Pharmacology
    Volume398
    Issue number2
    DOIs
    Publication statusPublished - 2000 Jun 16

    Keywords

    • Ca channel
    • Death
    • Hippocampal neuron
    • Na channel
    • Swelling
    • Veratridine

    ASJC Scopus subject areas

    • Pharmacology

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