Cardioprotective Effect of Opioids, Derivatives of Amide N-Methyl-2-(Pirrolidin-1-yl)Cyclohexyl-1-Amine, under Conditions of Ischemia/Reperfusion of the Heart

Bull Exp Biol Med. 2021 Apr;170(6):710-713. doi: 10.1007/s10517-021-05138-y. Epub 2021 Apr 24.

Abstract

We performed a comparative analysis of infarction-limiting activity of analogues of opioid receptor agonist U-50488 under conditions of heart reperfusion in rats. Derivatives of amide N-methyl-2-(pyrrolidin-1-yl)cyclohexyl-1-amine were administered 5 min before reperfusion in a dose of 1 mg/kg, derivative II (opicor) was additionally used in a dose of 2 mg/kg. In a dose of 1 mg/kg, all derivatives of opioid U-50488 were ineffective and produced no infarction-limiting effect. Opicor in a dose of 2 mg/kg reduced the infarction size/area at risk ratio and improved the contractility parameters of the isolated heart. Opioid receptor antagonist naltrexone (5 mg/kg) abolished the infarction-limiting effect of opicor. Hence, the infarction-reducing effect of opicor is associated with activation of opioid receptors. We also demonstrated that the opioid (opicor) can improve cardiac contractility during the reperfusion period.

Keywords: heart; opioids; postconditioning; reperfusion.

MeSH terms

  • Amides / chemistry*
  • Amines / chemistry*
  • Amines / therapeutic use*
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Cardiotonic Agents / chemistry
  • Cardiotonic Agents / therapeutic use
  • Heart / drug effects
  • Male
  • Myocardial Reperfusion Injury / drug therapy*
  • Narcotic Antagonists / chemistry
  • Narcotic Antagonists / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / metabolism

Substances

  • Amides
  • Amines
  • Analgesics, Opioid
  • Cardiotonic Agents
  • Narcotic Antagonists
  • Receptors, Opioid