Dual Enkephalinase Inhibitors and Their Role in Chronic Pain Management

Curr Pain Headache Rep. 2021 Mar 24;25(5):29. doi: 10.1007/s11916-021-00949-0.

Abstract

Purpose of review: Dual enkephalinase inhibitors (DENKIs) are pain medications that indirectly activate opioid receptors and can be used as an alternative to traditional opioids. Understanding the physiology of enkephalins and their inhibitors and the pharmacology of these drugs will allow for proper clinical application for chronic pain patients in the future.

Recent findings: DENKIs can be used as an alternative mode of analgesia for patients suffering from chronic pain by preventing the degradation of endogenous opioid ligands. By inhibiting the two major enkephalin-degrading enzymes (neprilysin and aminopeptidase N), DENKIs can provide analgesia with less adverse effects than nonendogenous opioids. The purpose of this paper is to review the current literature investigating DENKIs and explore their contribution to chronic pain management.

Keywords: Analgesia; Chronic pain; Endogenous opioid; Enkephalinase inhibitors; Multimodal analgesia; Pain management.

Publication types

  • Review

MeSH terms

  • CD13 Antigens / antagonists & inhibitors*
  • Chronic Pain / drug therapy*
  • Dipeptides / therapeutic use
  • Disulfides / therapeutic use*
  • Enkephalins / metabolism*
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Neprilysin / antagonists & inhibitors*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / therapeutic use
  • Propionates / therapeutic use*
  • Propylamines / therapeutic use*

Substances

  • 1-(2-((1-ethoxycarbonyloxyethoxycarbonylmethyl)carbamoyl)-3-phenylpropyldisulfanylmethyl)-3-methylsulfanylpropylamine
  • Dipeptides
  • Disulfides
  • Enkephalins
  • Enzyme Inhibitors
  • PL265
  • Propionates
  • Propylamines
  • RB 101
  • kelatorphan
  • Phenylalanine
  • CD13 Antigens
  • Neprilysin