On the Mechanism of the Cardioprotective Action of σ1 Receptor Agonist Anxiolytic Fabomotizole Hydrochloride (Afobazole)

Bull Exp Biol Med. 2018 Sep;165(5):660-664. doi: 10.1007/s10517-018-4236-1. Epub 2018 Sep 17.

Abstract

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.

Keywords: Afobazole; Epac2 protein; echocardiography; receptors; translational rat model of chronic heart failure.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Animals, Outbred Strains
  • Anti-Anxiety Agents / pharmacology
  • Benzimidazoles / pharmacology*
  • Biomarkers / blood
  • Cardiotonic Agents / pharmacology*
  • Coronary Occlusion / drug therapy*
  • Coronary Occlusion / genetics
  • Coronary Occlusion / physiopathology
  • Coronary Vessels / surgery
  • Drug Administration Schedule
  • Drug Repositioning
  • Gene Expression Regulation / drug effects
  • Guanine Nucleotide Exchange Factors / antagonists & inhibitors
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Heart Failure / genetics
  • Heart Failure / physiopathology
  • Heart Failure / prevention & control*
  • Male
  • Morpholines / pharmacology*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Natriuretic Peptide, Brain / antagonists & inhibitors
  • Natriuretic Peptide, Brain / blood
  • Rats
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Vasopressin / genetics
  • Receptors, Vasopressin / metabolism

Substances

  • 2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole
  • Angiotensin II Type 1 Receptor Blockers
  • Anti-Anxiety Agents
  • Benzimidazoles
  • Biomarkers
  • Cardiotonic Agents
  • Guanine Nucleotide Exchange Factors
  • Morpholines
  • Rapgef4 protein, rat
  • Receptor, Angiotensin, Type 1
  • Receptors, Glucocorticoid
  • Receptors, Vasopressin
  • V1a vasopressin receptor, rat
  • Natriuretic Peptide, Brain