On the mechanism of anti-ischemic effects of afobazole.

Abstract

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.

• Authors: S B Seredenin, I B Tsorin, M B Vititnova, V N Stolyaruk, G G Chichkanov, S A Kryzhanovskii
• Journal: Bulletin of experimental biology and medicine (Bull Exp Biol Med) Vol. 155 Issue 6 Pg. 760-3 (Oct 2013) ISSN: 1573-8221 [Electronic] United States
• PMID: 24288760 (Publication Type: Journal Article)

Chemical References

• 2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole
• Anti-Arrhythmia Agents
• Benzimidazoles
• Cardiotonic Agents
• Morpholines
• Verapamil

Topics

• Administration, Intravenous
• Animals
• Animals, Outbred Strains
• Anti-Arrhythmia Agents (pharmacology, therapeutic use)
• Benzimidazoles (administration & dosage)
• Cardiotonic Agents (administration & dosage)
• Drug Evaluation, Preclinical
• Drug Therapy, Combination
• Male
• Morpholines (administration & dosage)
• Myocardial Contraction (drug effects)
• Myocardial Ischemia (drug therapy, physiopathology)
• Rats
• Verapamil (pharmacology, therapeutic use)