TY - JOUR
T1 - T-477, a novel Ca2+- and Na+ channel blocker, prevents veratridine-induced neuronal injury
AU - Okuyama, Kayoko
AU - Kiuchi, Satoko
AU - Okamoto, Masahito
AU - Narita, Hiroshi
AU - Kudo, Yukitsuka
PY - 2000/6/16
Y1 - 2000/6/16
N2 - 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.
AB - 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.
KW - Ca channel
KW - Death
KW - Hippocampal neuron
KW - Na channel
KW - Swelling
KW - Veratridine
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U2 - 10.1016/S0014-2999(00)00305-8
DO - 10.1016/S0014-2999(00)00305-8
M3 - Article
C2 - 10854832
AN - SCOPUS:0034674664
VL - 398
SP - 209
EP - 216
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -