RH-3421, a potent dihydropyrazole insecticide, inhibits depolarization-stimulated rises in free [Ca2+] and 45Ca2+ uptake in mammalian synaptosomes.

Abstract

The dihydropyrazole RH-3421 inhibits veratridine- and K(+)-induced rises in synaptosomal free Ca2+ with IC50s of 0.2 and 1 microM, respectively. The K(+)-induced rise in free synaptosomal Ca2+, which requires external Ca2+, is also blocked by RH-3421 in the presence of tetrodotoxin. The K(+)-stimulated 45Ca2+ uptake by synaptosomes is unaffected by tetrodotoxin, blocked by cobalt ions and inhibited by RH-3421 both alone (IC50 = 11 microM) and in the presence of tetrodotoxin. RH-3421 does not influence the level of free Ca2+ or basal 45Ca2+ uptake in non-depolarized synaptosomes. The results suggest RH-3421 inhibits voltage-sensitive calcium channels in nerve endings.