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Differences between and combinations of opioids re-visited
1Centre for Integrated Preclinical Drug Development and School of Pharmacy, University of Queensland, St Lucia Campus, Brisbane, Queensland, Australia. maree.smith@uq.edu.au
Purpose Of Review:
Recent studies highlighting between-opioid differences in patient outcomes, opioid receptor interactions and animal study findings implicating a 'fine control' mechanism underpinning potential diversity in opioid receptor signalling that could potentially be exploited to develop novel opioid analgesics with improved tolerability are reviewed.
Recent Findings:
Recent clinical trials confirm the success of 'opioid rotation' for improving opioid tolerability and restoring analgesia in most patients who would otherwise experience intolerable side effects and poor pain relief. These findings suggest that individual strong opioids may interact, at least in part, with different opioid receptor sub-populations or modulate mu opioid receptor signalling in subtly different ways. Identification of novel mu opioid splice variants with different intron 1 sizes that heterodimerize with, and modulate the function of, native mu opioid receptors provide insight into potential diversity in opioid signalling. Oxycodone, unlike other strong opioids, does not cause potassium current desensitization nor does it displace [3H]-morphine binding, consistent with its different in-vivo pharmacological profile to morphine. Opioid analgesic combinations administered as tethered bivalent ligands or admixture demonstrate good pain relief with improved side effect profiles.
Summary:
Enhanced understanding of diversity in opioid signalling has the potential to produce novel strong opioid analgesics with improved tolerability.
Insights
Understanding opioid receptor signaling diversity can lead to new pain relief medications. Research shows different opioids have unique effects, offering hope for better tolerability and pain management.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Management
Background:
- Opioid analgesics are crucial for pain management but often cause significant side effects.
- Recent research suggests variability in opioid receptor interactions and signaling pathways.
Purpose of the Study:
- To review current findings on between-opioid differences in patient outcomes and receptor interactions.
- To explore the potential for developing novel opioid analgesics with improved tolerability based on signaling diversity.
Main Methods:
- Review of recent clinical trials and animal study findings.
- Analysis of opioid receptor signaling mechanisms, including splice variants and heterodimerization.
- Pharmacological comparison of different strong opioids, such as oxycodone and morphine.
Main Results:
- Opioid rotation is effective in improving tolerability and analgesia for many patients.
- Individual opioids may interact with different receptor sub-populations or modulate signaling uniquely.
- Novel mu opioid splice variants influence native receptor function, indicating signaling diversity.
- Oxycodone exhibits a distinct in-vivo pharmacological profile compared to morphine.
- Combined opioid analgesics show promise for effective pain relief with fewer side effects.
Conclusions:
- Understanding opioid signaling diversity is key to developing safer and more effective opioid analgesics.
- Exploiting these differences could lead to novel pain management strategies with improved patient tolerability.
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