Investigational drugs targeting the prostaglandin E2 signaling pathway for the treatment of inflammatory pain

Expert Opin Investig Drugs. 2017 Jan;26(1):51-61. doi: 10.1080/13543784.2017.1260544. Epub 2016 Nov 20.

Abstract

Non-steroidal anti-inflammatory drugs (NSAID) are the most commonly used drugs for the treatment of pain, inflammation and fever. Although they are effective for a huge number of users, their analgesic properties are not sufficient for several patients and the occurrence of side effects still constitutes a big challenge during long term therapy. Areas covered: This review gives an overview about the first and second generations of NSAIDs (COX1/2 non-selective, COX-2 selective), and their main side effects which gave still an urgent need for safer drugs and for the establishment of novel treatment strategies (improved safety, tolerability, patient convenience). The current developments of a possible third generation NSAID class comprise changes in the formulation of already approved drugs, combination therapies, dual cyclooxygenase-lipoxygenase inhibitors, NO- and H2S-releasing NSAIDs, prostaglandin synthase inhibitors and EP receptor modulators, respectively. Literature search has been done with PubMed NCBI. Expert opinion: Currently, there is no newly developed drug that is superior to the already approved selective and non-selective NSAIDs. Several novel approaches show promising analgesic efficacy but side effects are still an important problem. Solutions might be constituted by combination therapies allowing administration of lower drug doses or by individualized therapies targeting molecules apart from COX, respectively.

Keywords: NSAID; cyclooxygenase; prostaglandins; proton pump inhibitor; side effects.

Publication types

  • Review

MeSH terms

  • Analgesics / adverse effects
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / pharmacology
  • Cyclooxygenase Inhibitors / therapeutic use
  • Dinoprostone / metabolism
  • Drug Design
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Pain / drug therapy*
  • Pain / physiopathology
  • Signal Transduction / drug effects

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Drugs, Investigational
  • Dinoprostone