ArticleBritish journal of pharmacology2014
Buprenorphine signalling is compromised at the N40D polymorphism of the human μ opioid receptor in vitro.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of their influence on plasma methadone levels and clinical response to methadone maintenance treatment in opioid use disorder.Fundamental & clinical pharmacology · 2025Article
- Receptor Pharmacogenomics: Deciphering Genetic Influence on Drug Response.International journal of molecular sciences · 2024Review
- Tapentadol shows lower intrinsic efficacy at µ receptor than morphine and oxycodone.Pharmacology research & perspectives · 2022Article
- Loss of SUR1 subtype KBehavioural brain research · 2021Article
- Buprenorphine Increases HIV-1 Infection In Vitro but Does Not Reactivate HIV-1 from Latency.Viruses · 2021Article
- A review of the existing literature on buprenorphine pharmacogenomics.The pharmacogenomics journal · 2021Review
- Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism.Current oncology reports · 2020Review
- The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors.PLoS computational biology · 2018Article
- Convergent Balancing Selection on the Mu-Opioid Receptor in Primates.Molecular biology and evolution · 2017Article
- Genetic variation in the behavioral effects of buprenorphine in female mice derived from a murine model of the OPRM1 A118G polymorphism.Neuropharmacology · 2017Article
- The switch from buprenorphine to tapentadol: is it worth?Romanian journal of anaesthesia and intensive care · 2016Review
- Receptor Reserve Moderates Mesolimbic Responses to Opioids in a Humanized Mouse Model of the OPRM1 A118G Polymorphism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Mouse model of OPRM1 (A118G) polymorphism has altered hippocampal function.Neuropharmacology · 2015Article
- A6V polymorphism of the human μ-opioid receptor decreases signalling of morphine and endogenous opioids in vitro.British journal of pharmacology · 2015Article
- Pharmacogenomics of buprenorphine - a narrative review.PharmacogenomicsReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThere is significant variation in individual response to opioid drugs, which may result in inappropriate opioid therapy. Polymorphisms of the μ opioid receptor (MOP receptor) may contribute to individual variation in opioid response by affecting receptor function, and the effect may be ligand-specific. We sought to determine functional differences in MOP receptor signalling at several signalling pathways using a range of structurally distinct opioid ligands in cells expressing wild-type MOP receptors (MOPr-WT) and the commonly occurring MOP receptor variant, N40D. EXPERIMENTAL APPROACH: MOPr-WT and MOPr-N40D were stably expressed in CHO cells and in AtT-20 cells. Assays of AC inhibition and ERK1/2 phosphorylation were performed on CHO cells, and assays of K activation were performed on AtT-20 cells. Signalling profiles for each ligand were compared between variants. KEY
resultsBuprenorphine efficacy was reduced by over 50% at MOPr-N40D for AC inhibition and ERK1/2 phosphorylation. Buprenorphine potency was reduced threefold at MOPr-N40D for K channel activation. Pentazocine efficacy was reduced by 50% for G-protein-gated inwardly rectifying K channel activation at MOPr-N40D. No other differences were observed for any other ligands tested. CONCLUSIONS AND IMPLICATIONS: The N40D variant is present in 10-50% of the population. Buprenorphine is a commonly prescribed opioid analgesic, and many individuals do not respond to buprenorphine therapy. This study demonstrates that buprenorphine signalling to several effectors via the N40D variant of MOP receptors is impaired, and this may have important consequences in a clinical setting for individuals carrying the N40D allele.
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