Related Experiment Video
Updated: Feb 5, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Designing safer analgesics: a focus on μ-opioid receptor pathways
Joseph V Pergolizzi1, Jo Ann LeQuang1, Robert Taylor1
1a NEMA Research, Inc , Naples , FL , USA.
Introduction:
The recent dramatic increase in intentional and unintentional deaths attributed to opioids has refocused attention on the therapeutic ratio (risk-benefit ratio) of opioid analgesics. Almost all traditional opioid analgesics produce their effects (therapeutic and adverse) via the activation of μ-opioid receptor (MOR) pathways. It is therefore important to examine the question of whether this natural endogenous pathway can still be activated, but with greater safety. Areas covered: Other comprehensive reviews have focused on pharmacokinetic (e.g. peripheral restriction) and pharmacodynamic (e.g. functional selectivity, biased ligand) approaches. Herein, the authors focus on a different approach, specifically, multi-mechanistic 'atypical opioids' that synergistically combines MOR activation plus one or more non-opioid mechanism of analgesic action. Expert opinion: Four 'atypical opioid' analgesics on the market act as μ-opioid receptor pathway agonists but have a non-opioid mechanism of action that significantly contributes to the analgesic effect. The multi-mechanistic action of these products confers particular clinical utility in that they provide effective analgesia with relatively lower opioid load, and they are generally associated with fewer or less severe opioid-related adverse effects and less abuse compared to traditional opioid analgesics.
Insights
Atypical opioids combine μ-opioid receptor (MOR) activation with non-opioid pathways for safer pain relief. These multi-mechanistic analgesics offer effective pain management with reduced opioid load, adverse effects, and abuse potential.
Area of Science:
- Pharmacology
- Pain Management
- Drug Development
Background:
- Rising opioid-related deaths necessitate improved analgesic safety profiles.
- Traditional opioids primarily act via μ-opioid receptor (MOR) pathways, leading to significant risks.
- Exploring alternative opioid analgesics with enhanced therapeutic ratios is crucial.
Purpose of the Study:
- To examine multi-mechanistic 'atypical opioids' as a safer alternative to traditional analgesics.
- To focus on synergistic combinations of MOR activation and non-opioid analgesic mechanisms.
- To evaluate the clinical utility and safety of atypical opioids.
Main Methods:
- Review of existing literature on opioid analgesics and novel approaches.
- Focus on multi-mechanistic drugs combining MOR agonism with non-opioid actions.
- Analysis of pharmacokinetic and pharmacodynamic strategies for safer opioid therapy.
Main Results:
- Four marketed atypical opioids activate MOR pathways alongside non-opioid mechanisms.
- These atypical opioids provide effective analgesia with a lower opioid load.
- They are associated with fewer/less severe opioid-related adverse effects and reduced abuse potential.
Conclusions:
- Multi-mechanistic atypical opioids represent a promising advancement in pain management.
- Their combined MOR and non-opioid actions enhance safety and efficacy.
- These agents offer a reduced-risk profile compared to traditional opioid analgesics.
More Related Videos
Related Concept Videos
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
01:22Opioid Receptors: Overview
01:28Insulin: The Receptor and Signaling Pathways
01:00Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
02:01Group Design