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Comparative Analysis of Infarct-Limiting Activity of Peptide and Non-Peptide δ- and κ-Opioid Receptor Agonists during Heart Reperfusion In Vivo

  • A. V. Mukhomedzyanov,
  • S. V. Popov,
  • A. S. Gorbunov,
  • N. V. Naryzhnaya,
  • V. N. Azev,
  • V. V. Kolpakov,
  • E. A. Tomilova,
  • E. V. Sapozhenkova,
  • L. N. Maslov

摘要

A comparative analysis of the infarct-limiting activity of δ- and κ-opioid receptors (OR) agonists was carried out on a model of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used selective δ2-OR agonist deltorphin II (0.12 mg/kg), δ-OR agonists BW373U86 and p-Cl-Phe DPDPE (0.1 and 1 mg/kg), selective agonists of δ1-OR DPDPE (0.1 and 0.969 mg/kg), κ1-OR U-50,488 (0.1 and 1 mg/kg), κ2-OR GR-89696 (0.1 mg/kg), and κ-OR ICI-199,441 (0.1 mg/kg). All drugs were administered intravenously 5 min before reperfusion. Deltorphin II, BW373U86 (1 mg/kg), p-Cl-Phe DPDPE (1 mg/kg), U-50,488 (1 mg/kg), and ICI-199,441 had a cardioprotective effect. The most promising compounds for drug development are ICI-199,441 and deltorphin II.