2. Academic Validation
  3. Progress in the development of more effective and safer analgesics for pain management

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

  • Eur J Med Chem. 2019 Dec 1:183:111701. doi: 10.1016/j.ejmech.2019.111701.
Rita Turnaturi 1,  Santina Chiechio 2,  Loredana Salerno 3,  Antonio Rescifina 4,  Valeria Pittalà 3,  Giuseppina Cantarella 5,  Emilia Tomarchio 6,  Carmela Parenti 7,  Lorella Pasquinucci 3
Affiliations

Affiliations

  • 1 Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy. Electronic address: rita.turnaturi@unict.it.
  • 2 Department of Drug Sciences, Pharmacology and Toxicology Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy; Oasi Research Institute-IRCCS, Troina, Italy.
  • 3 Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
  • 4 Department of Drug Sciences, Chemistry Section, University of Catania, Viale A. Doria, 95125, Catania, Italy.
  • 5 Department of Biomedical and Biotechnological Sciences, Pharmacology Section, University of Catania, Catania, Italy.
  • 6 1° Clinica Ortopedica, ASST Gaetano Pini-CTO, Milan, Italy.
  • 7 Department of Drug Sciences, Pharmacology and Toxicology Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
PMID: 31550662 DOI: 10.1016/j.ejmech.2019.111701
Abstract

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.

Keywords

Analgesia; Delta opioid receptor; Kappa opioid receptor; Mu opioid receptor; SAR.

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