The anti-ischemic effect of synthetic and pharmacologically tested anxiolytic afobazole (10 mg/kg intravenously) was studied on anesthetized rats with acute endocardial ischemia caused by isoproterenol infusion (20 mg/kg/min). A calcium antagonist verapamil (1 mg/kg intravenously) belonging to the group of phenyl alkyl amine derivatives was used as the reference drug. Afobazole and verapamil were shown to exhibit anti-ischemic activity in this experimental model, which was seen from significant decrease in ST segment depression on ECG. The neuroprotective effect of afobazole is to a great extent related to its affinity for σ1 receptors. Therefore, a special series was performed to evaluate the anti-ischemic effect of afobazole after blockade of these receptors with haloperidol (0.5 mg/kg intravenously). Afobazole exhibited no anti-ischemic activity under these conditions. σ1 receptor blockade had no effect on anti-ischemic activity of verapamil. Our results suggest that the agonistic effect of afobazole on σ1 receptors in cardiomyocytes contributes to anti-ischemic activity of this agent.