ArticleBritish journal of pharmacology2019
Functional characterization of a novel opioid, PZM21, and its effects on the behavioural responses to morphine.
Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.Psychopharmacology · 2024Article
- Opioid system and related ligands: from the past to future perspectives.Journal of anesthesia, analgesia and critical care · 2024Review
- Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage.Science advances · 2024Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids.Acta pharmaceutica Sinica. B · 2023Article
- Structure-Based Evolution of G Protein-Biased μ-Opioid Receptor Agonists.Angewandte Chemie (International ed. in English) · 2022Article
- Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology.Pharmacology & therapeutics · 2022Review
- Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies.Pharmaceutics · 2021Article
- Influence of G protein-biased agonists of μ-opioid receptor on addiction-related behaviors.Pharmacological reports : PR · 2021Review
- Discovery of μ,δ-Opioid Receptor Dual-Biased Agonists That Overcome the Limitation of Prior Biased Agonists.ACS pharmacology & translational science · 2021Article
- Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.eLife · 2021Article
- Biased Opioid Ligands: Revolution or Evolution?Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Optimizing Perioperative Use of Opioids: A Multimodal Approach.Current anesthesiology reports · 2020Article
- Molecular Modeling of µ Opioid Receptor Ligands with Various Functional Properties: PZM21, SR-17018, Morphine, and Fentanyl-Simulated Interaction Patterns Confronted with Experimental Data.Molecules (Basel, Switzerland) · 2020Article
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- Biased versus Partial Agonism in the Search for Safer Opioid Analgesics.Molecules (Basel, Switzerland) · 2020Review
- Functional characterization of a novel opioid, PZM21, and its effects on the behavioural responses to morphine.British journal of pharmacology · 2019Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe concept of opioid ligands biased towards the G protein pathway with minimal recruitment of β-arrestin-2 is a promising approach for the development of novel, efficient, and potentially nonaddictive opioid therapeutics. A recently discovered biased μ-opioid receptor agonist, PZM21, showed analgesic effects with reduced side effects. Here, we aimed to further investigate the behavioural and biochemical properties of PZM21. EXPERIMENT APPROACH: We evaluated antinociceptive effects of systemic and intrathecal PZM21 administration. Its addiction-like properties were determined using several behavioural approaches: conditioned place preference, locomotor sensitization, precipitated withdrawal, and self-administration. Also, effects of PZM21 on morphine-induced antinociception, tolerance, and reward were assessed. Effects of PZM21 on striatal release of monoamines were evaluated using brain microdialysis. KEY
resultsPZM21 caused long-lasting dose-dependent antinociception. It did not induce reward- and reinforcement-related behaviour; however, its repeated administration led to antinociceptive tolerance and naloxone-precipitated withdrawal symptoms. Pretreatment with PZM21 enhanced morphine-induced antinociception and attenuated the expression of morphine reward. In comparison to morphine, PZM21 administration induced a moderate release of dopamine and a robust release of 5-HT in the striatum. CONCLUSIONS AND IMPLICATIONS: PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties. However, its clinical application may be restricted, as it induces tolerance and withdrawal symptoms. Notably, its ability to diminish morphine reward implies that PZM21 may be useful in treatment of opioid use disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.