On the mechanism of antifibrillatory effect of afobazole.
Effect of afobazole on the threshold of electrical fibrillation of the heart was studied on anesthetized rats with intact myocardium. It was shown that the drug considerably increased the threshold of electrical fibrillation of the heart, being not inferior to reference class I antiarrhythmic drugs (lidocaine and procainamide) according to V. Williamse classification. Against the background of preliminary injection of σ-receptor antagonist haloperidol, afobazole exhibited no antifibrillatory activity. These findings and analysis of published reports suggest that antifibrillatory activity of afobazole is determined by its antagonistic influence on σ1-receptors localized in cardiomyocyte cytosol.
V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia. sak538@yandex.ru
S A
SA
Kryzhanovskyi
V N
VN
Stolyaruck
M B
MB
Vititnova
I B
IB
Tsorin
S B
SB
Seredenin
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism* / Q000494:pharmacology; D001562:Benzimidazoles / Q000378:metabolism* / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009025:Morpholines / Q000378:metabolism* / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000188:drug therapy*
C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; D000889:Anti-Arrhythmia Agents; D001562:Benzimidazoles; D009025:Morpholines; D017480:Receptors, sigma; D006220:Haloperidol