Inhibitory Effects of Tetrahydroisoquisoquinoline Derivatives on Ca²⁺ and Na⁺Channels in Crude Nerve Endings

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Semi-synthetic tetrahydroisoquinoline derivatives prepared from natural alkaloids, possess Ca²⁺ antagonistic properties. These derivatives significantly blocked KCl-stimulated Ca²⁺ uptake (In chick and rat crude nerve ending) which can be partially inhibited by the selective N-type Ca²⁺ channel blocker ω-conotoxin GVIA or the selective P-type Ca²⁺ channel blocker ω-agatoxin IVA. Moreover, PX42 (10 μM; for the tetrahydroisoquinoline compounds in this study) could inhibit the activity of calmodulin-dependent phosphodiesterase and block veratridine-induced (or tetrodotoxin-sensitive) Na⁺ uptake. The possible mechanism(s) of non-selective inhibition of ion channels of PX42 is discussed.