Progress in the development of more effective and safer analgesics for pain management

Rita Turnaturi, Santina Chiechio, Loredana Salerno, Antonio Rescifina, Valeria Pittalà, Giuseppina Cantarella, Emilia Tomarchio, Carmela Parenti, Lorella Pasquinucci

Research output: Contribution to journalReview articlepeer-review


Opioid analgesics have been used for thousands of years in the treatment of pain and related disorders, and have become among the most widely prescribed medications. Among opioid analgesics, mu opioid receptor (MOR) agonists are the most commonly used and are indicated for acute and chronic pain management. However, their use results in a plethora of well-described side-effects. From selective delta opioid receptor (DOR) and kappa opioid receptor (KOR) agonists to multitarget MOR/DOR and MOR/KOR ligands, medicinal chemistry provided different approaches aimed at the development of opioid analgesics with an improved pharmacological and tolerability fingerprint. The emergent medicinal chemistry strategy to develop ameliorated opioid analgesics is based upon the concept that functional selectivity for G-protein signalling is necessary for the therapeutic effect, whether β-arrestin recruitment is mainly responsible for the manifestation of side effects, including the development of tolerance after repeated administrations. This review summarises most relevant biased MOR, DOR, KOR and multitarget MOR/DOR ligands synthesised in the last decade and their pharmacological profile in “in vitro” and “in vivo” studies. Such biased ligands could have a significant impact on modern drug discovery and represent a new strategy for the development of better-tolerated drug candidates.

Original languageEnglish
Article number111701
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Dec 1 2019


  • Analgesia
  • Delta opioid receptor
  • Kappa opioid receptor
  • Mu opioid receptor
  • SAR

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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