Synthesis and Infarction-Limiting Properties of Peptide Agonists of Opioid Receptors

Abstract

Three structurally different peptide agonists of opioid receptors, i.e., gludalan, deltolei, and dalargin, were synthesized and assessed for infarction-limiting effects in rats with coronary occlusion (45 min) and reperfusion (2 h). The opioid peptides dalargin and gludalan (0.1 mg/kg) and deltolei (0.03, 0.1, and 0.2 mg/kg) were injected 5 min before reperfusion. It was found that gludalan and deltolei at a dose of 0.1 mg/kg decreased the ratio of infarction size to the area at risk (IS/AAR) whereas dalargin did not affect the IS. The infarction-limiting effect of deltolei disappeared if the peptide dose was decreased (0.03 mg/kg) or increased (0.2 mg/kg). The opioid receptor antagonists naltrexone (5 mg/kg) or naloxone methiodide (5 mg/kg), which does not penetrate the blood—brain barrier, eliminated the infarction-limiting effect of gludalan.