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The goal of this study was to examine effects of a novel galanin receptor agonist GalR1-3  [bAla14, His15]-galanine 2-15 (G), obtained by automatic solid-phase synthesis, on the metabolic state of the area at risk  and the size of acute myocardial infarction (MI) in rats in vivo and evaluate its toxicity in BALB /c mice. In anesthetized  rats, regional ischemia was simulated by coronary artery occlusion and then coronary blood flow was restored.  The peptide G was administered intravenously (i.v.) with a bolus after a period of regional ischemia in the dose range  of 0.25-3.0 mg/kg. The sizes of MI and the activities of creatine kinase-MB (СK-MB) and lactate dehydrogenase (LDH)  in blood plasma were estimated. The effect of administration of the optimal dose of G (1.0 mg/kg) on myocardial content  of adenine nucleotides (AN), phosphocreatine (PCr), creatine (Cr) and lactate was studied. I.v. administration of G  to rats at a dose of 1.0 mg/kg slightly affected hemodynamic parameters, but reduced MI size by 40% and decreased  plasma LDH and CK-MB activity by the end of reperfusion compared to control. These effects were  accompanied by a significant improvement in energy state of area at risk (AAR) – an increase in myocardial content  of ATP, åAN, PCr and åCr, and combined with a decrease in myocardial lactate level compared with the control.  Toxicity of peptide G was studied with a single intraperitoneal injection of 0.5-3.0% solution of the peptide  substance to mice. The absence of signs of intoxication and death of animals after G injection in the maximum  possible dose did not allow determining the value of the average lethal dose. The results indicate therapeutic  potential of the peptide G for preventing myocardial ischemia and reperfusion injury and feasibility for further study  of its pharmacological properties and mechanisms of action.

Cardiometabolic efficacy and toxicological evaluation of a pharmacological galanin receptor agonist