Animal experiment:

Rats[2]8-week-old male spf Wistar rats are used. Rats are anaesthetized with Thiobarbiturate inactin (BYK, 100 mg/kg, i.p.). The interaction of the ventilatory response to hypoxia and an intermittent (2 min on, 1 min break) low-dose (10 μg/kg per min) and high-dose (80 μg/kg per min) infusion of S9581 or Almitrine is tested in control and chronically hypoxic rats. S9581 or Almitrine is infused intravenously (100 μg/ mL). Inspired oxygen levels were controlled by passing oxygen-nitrogen mixtures across the tracheal port at a flow rate of 3-41 min-1[2].

Almitrine mesylate, a peripheral chemoreceptor agonist, inhibits selectively the Ca2+-dependent K+ channel.

Almitrine inhibits the activity of a high-conductance (152±13 pS), Ca2+-dependent K+ channel by decreasing its open probability. The IC50 value of the effect is 0.22 μM. The inhibitory effect of Almitrine on Ca2+-dependent K+ channels also is observed in GH3 cells. Almitrine at concentrations up to 10 μM does not affect whole-cell voltage-dependent K+, Ca2+, or Na+ currents in rat or rabbit cells. However, this concentration of Almitrine significantly inhibits the Ca2+-dependent component of K+ currents in rat chemoreceptor cells[1].

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[2].

[1]. López-López JR, et al. Effects of Almitrine bismesylate on the ionic currents of chemoreceptor cells from the carotid body. Mol Pharmacol. 1998 Feb;53(2):330-9. [2]. Bee D, et al. An analysis of the action of an analogue of Almitrine bismesylate in the rat model of hypoxic lung disease. Exp Physiol. 1992 Nov;77(6):819-28.