sm-346 and Myocardial-Ischemia

Anti-ischemic activity of fabomotizole hydrochloride was studied on the model of subendocardial ischemia in rats with endothelial dysfunction. Endothelial dysfunction was modeled by intragastric administration of methionine (3 g/kg, once a day for 7 days). Acute subendocardial ischemia was induced in narcotized rats by intraperitoneal injection of isoproterenol (20 μg/kg/min over 5 min). Fabomotizole hydrochloride (intraperitoneally, 15 mg/kg) significantly reduced isoproterenol-induced ST segment depression in animals with endothelial dysfunction and with intact vasculature.

Topics: Animals; Animals, Outbred Strains; Benzimidazoles; Cardiotonic Agents; Disease Models, Animal; Endocardium; Endothelium, Vascular; Isoproterenol; Male; Methionine; Morpholines; Myocardial Ischemia; Rats; Treatment Outcome

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.

Topics: Administration, Intravenous; Animals; Animals, Outbred Strains; Anti-Arrhythmia Agents; Benzimidazoles; Cardiotonic Agents; Drug Evaluation, Preclinical; Drug Therapy, Combination; Male; Morpholines; Myocardial Contraction; Myocardial Ischemia; Rats; Verapamil