Mechanisms Underlying the Antiarrhythmic Action of Compound ALM-802

Abstract

The mechanisms underlying the antiarrhythmic action of compound trihydrochloride N¹-(2,3,4-trimethoxy)-N²-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethane-diamine (code ALM-802) were studied in vitro. The experiments were performed on a culture of rat hippocampal neurons. The electrical activity of neurons was recorded by the patch-clamp method in the whole cell configuration. It is shown that the compound ALM-802 effectively blocks potential-dependent Na⁺ and K⁺ channels and does not affect the activity of potential-dependent Ca²⁺ channels. The inhibition of currents through these channels is dose-dependent; the IC₅₀ of Na⁺ and K⁺ channels were 94±4 and 67±3 μM, respectively. These findings indicate that compound ALM-802 combines the properties of class I and class III antiarrhythmic agents according to the Vaughan-Williams classification.

Keywords: Ca2+ channels; K+ channels; Na+ channels; compound ALM-802; patch-clamp.