sm-346 and Myocardial-Infarction

Original translational rat model of chronic heart failure provoked by experimental anterior transmural myocardium infarction was employed to examine the preventive action of anxiolytic Afobazole (15 mg/kg/day administered intraperitoneally during the first 15 days after coronary occlusion) on the development of the heart failure assessed in 3 months after infarction. Afobazole prevented the development of pathologic remodeling of the myocardium, maintained its inotropic function, and decreased the plasma level of brain natriuretic peptide known as a biochemical marker of chronic heart failure. In the myocardium, Afobazole down-regulated overexpression of the genes induced in chronic heart failure and assessed by corresponding RNA levels, which code angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as well as Epac2 protein. The revealed biochemical changes are consistent with the data on cardioprotective action of Afobazole.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Animals, Outbred Strains; Anti-Anxiety Agents; Benzimidazoles; Biomarkers; Cardiotonic Agents; Coronary Occlusion; Coronary Vessels; Drug Administration Schedule; Drug Repositioning; Gene Expression Regulation; Guanine Nucleotide Exchange Factors; Heart Failure; Male; Morpholines; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Rats; Receptor, Angiotensin, Type 1; Receptors, Glucocorticoid; Receptors, Vasopressin

Delayed cardioprotective effects of anxiolytic Afobazole (15 mg/kg, intraperitoneally for 14 days) were evaluated using dynamic echocardiographic recordings on days 2, 15, 56, and 98 after experimental myocardial infarction modeling (rat model of acute myocardial ischemia). The cardiotropic activity of Afobazole is assumed to be related to its agonistic effects on σ

Topics: Animals; Benzimidazoles; Echocardiography; Heart Failure; Male; Morpholines; Myocardial Infarction; Rats; Stroke Volume; Ventricular Function, Left

The effect of nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA conjugates with arachidonic acid and docosahexaenoyl dopamine on the cerebral circulation has been studied in intact rats and those with global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. The most pronounced vasodilation activity in rats with global transient cerebral ischemia is exhibited by nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA-containing lipid derivatives. This effect of all these drugs (except for nimodipine) is not manifested on the background of GABA receptor blocker bicuculline. In rats with experimental myocardial infarction and combined vascular pathology of brain and heart not all of the compounds mentioned acbove with GABA-ergic mechanism of action stimulate the cerebral blood flow. Thus, both similarity and differences in cerebrovascular effects of these compounds have been found, which depend on the initial state of organism and the vascular pathology of brain and/or heart. The obtained results show good prospects for this direction of research.

Topics: Adamantane; Animals; Animals, Outbred Strains; Benzimidazoles; Bicuculline; Cerebral Cortex; Dopamine; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Ischemic Attack, Transient; Male; Melatonin; Morpholines; Myocardial Infarction; Nimodipine; Picolines; Rats; Receptors, GABA; Structure-Activity Relationship; Vasodilation; Vasodilator Agents

Seven-day treatment of rats with experimental myocardial infarction with afobazole (5-ethoxy-2-[2-morpholino)-ethylthio] benzimidasole dihydrochloride) resulted in shrinkage of the ischemic damage area in the heart, stimulation of reparative processes in the myocardium, and prevention of postinfarction remodeling of the left ventricle. Anti-ischemic effect of afobazole in experimental myocardial infarction is presumably due to its interactions with σ(1) receptors.

Topics: Animals; Benzimidazoles; Cell Proliferation; Male; Morpholines; Myocardial Infarction; Myocardium; Rats; Receptors, sigma; Statistics, Nonparametric; Ventricular Remodeling