Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion.

Abstract

We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of κ-opioid receptor agonists depended on activation of κ-opioid receptors.

• Authors: S Yu Tsibulnikov, L N Maslov, A V Mukhomedzyanov, A V Krylatov, M R Tsibulnikova, Yu B Lishmanov
• Journal: Bulletin of experimental biology and medicine (Bull Exp Biol Med) Vol. 159 Issue 6 Pg. 718-21 (Oct 2015) ISSN: 1573-8221 [Electronic] United States
• PMID: 26519268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Cardiotonic Agents
• Pyrrolidines
• Receptors, Opioid, kappa
• kappa(1) opioid receptor
• ICI 199441
• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer

Topics

• 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer (pharmacology, therapeutic use)
• Animals
• Anti-Arrhythmia Agents (pharmacology, therapeutic use)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Ischemic Preconditioning, Myocardial (methods)
• Myocardial Ischemia (drug therapy, pathology)
• Myocardial Reperfusion Injury (prevention & control)
• Pyrrolidines (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Receptors, Opioid, kappa (agonists)