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.

Publication date: Dec 01, 2019

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 ?-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.

Turnaturi, R., Chiechio, S., Salerno, L., Rescifina, A., , Pittal`a, Cantarella, G., Tomarchio, E., Parenti, C., and Pasquinucci, L. Progress in the development of more effective and safer analgesics for pain management. 04289. 2019 Eur J Med Chem (183):

Concepts Keywords
Analgesics Pain management
Arrestin Opioids
Chronic Pain Branches of biology
Delta Opioid Receptor Cell signaling
DOR Opioid receptors
Fingerprint Synthetic opioids
Functional Selectivity G protein-coupled receptors
G Protein Phenols
KOR Κ-opioid receptor
Ligands Δ-opioid receptor
MOR Morphinans
Opioid Functional selectivity
Opioid Receptor Cyclazocine
Pain
Pain Management
Pharmacological
Prescribed Medications
Tolerability

Semantics

Type Source Name
disease MESH development
disease MESH chronic pain
drug DRUGBANK Tropicamide

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