Almitrine inhibits the activity of a high-conductance (152±13 pS), Ca
2+
-dependent K
+
channel by decreasing its open probability. The IC
50
value of the effect is 0.22 μM. The inhibitory effect of Almitrine on Ca
2+
-dependent K
+
channels also is observed in GH3 cells. Almitrine at concentrations up to 10 μM does not affect whole-cell voltage-dependent K
+
, Ca
2+
, or Na
+
currents in rat or rabbit cells. However, this concentration of Almitrine significantly inhibits the Ca
2+
-dependent component of K
+
currents in rat chemoreceptor cells.
Almitrine acts via the peripheral arterial chemoreceptors raising carotid sinus nerve output and minute ventilation. Almitrine also has a pulmonary vascular action causing a dose-dependent constriction and dilatation. At low doses Almitrine enhances hypoxic pulmonary vasoconstriction and may improve the overall ventilation/perfusion ratio.
