Abstract
The effect of nilvadipine, a dihydropyridine derivative, on high-voltage activated (HVA) Ca2+ channels was investigated in freshly dissociated rat frontal cortical neurons. The cortical neurons were observed to have five pharmacologically distinct HVA Ca2+ channel subtypes consisting of the L-, N-, P-, O- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel current which comprised 23% of the total HVA Ca2+ channel current. A reversible inhibitory effect of nilvadipine on the L-type Ca2+ channel current was also observed in a concentration-dependent fashion without affecting the current-voltage relationship. The half-maximum inhibitory concentration was 3 x 10(-8) M. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca2+ influx, in combination with the cerebral vasodilatory action, may prevent neuronal damage during brain ischemia.
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