title: 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.affiliation: V. V. Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia. SAK-538@yandex.ru.
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
authors.forename: I B
authors.initials: IB
authors.lastname: Tsorin
authors.forename: M B
authors.initials: MB
authors.lastname: Vititnova
authors.forename: V N
authors.initials: VN
authors.lastname: Stolyaruk
authors.forename: G G
authors.initials: GG
authors.lastname: Chichkanov
authors.forename: S A
authors.initials: SA
authors.lastname: Kryzhanovskii
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D021461:Animals, Outbred Strains; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; D000889:Anti-Arrhythmia Agents; D001562:Benzimidazoles; D002316:Cardiotonic Agents; D009025:Morpholines; D014700:Verapamil