ArticleThe Journal of pharmacology and experimental therapeutics2012
P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 72 citations in OpenAlex.
- The Pharmacokinetics and Pharmacodynamics of Buprenorphine in Neonatal Abstinence Syndrome.Clinical pharmacology and therapeutics · 2018Trial
- Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.European journal of clinical pharmacology · 2016Trial
- Genome-Wide CRISPR Screens Identify ABCG2-Mediated Drug Resistance to the Threonine Tyrosine Kinase (TTK) Inhibitor CFI-402257 in Breast Cancer.International journal of molecular sciences · 2026Article
- Methadone and Buprenorphine as Medication for Addiction Treatment Diversely Affect Inflammation and Craving Depending on Their Doses.Pharmacy (Basel, Switzerland) · 2025Article
- Opioid metabolism and drug-drug interaction in cancer.The oncologist · 2024Review
- Reconsidering the usefulness of long-term high-dose buprenorphine.Frontiers in psychiatry · 2024Article
- An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Modulator Buprenorphine.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Detection, chemical analysis, and pharmacological characterization of dipyanone and other new synthetic opioids related to prescription drugs.Analytical and bioanalytical chemistry · 2023Article
- Maternal and Fetal Expression of ATP-Binding Cassette and Solute Carrier Transporters Involved in the Brain Disposition of Drugs.Advances in experimental medicine and biology · 2023Article
- EPD1504: a novel μ-opioid receptor partial agonist attenuates obsessive-compulsive disorder (OCD)-like behaviors.Frontiers in psychiatry · 2023Article
- Deuterated buprenorphine retains pharmacodynamic properties of buprenorphine and resists metabolism to the active metabolite norbuprenorphine in rats.Frontiers in pharmacology · 2023Article
- Findings from a pilot study of buprenorphine population pharmacokinetics: A potential effect of HIV on buprenorphine bioavailability.Drug and alcohol dependence · 2022Article
- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Identification of Potential Insect Growth Inhibitor againstInternational journal of molecular sciences · 2022Article
- Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.eLife · 2021Article
- Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study.Journal of personalized medicine · 2020Article
- Physiologically-Based Pharmacokinetic (PBPK) Modeling of Buprenorphine in Adults, Children and Preterm Neonates.Pharmaceutics · 2020Article
- A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain.Pain and therapy · 2020Review
- In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome.The Journal of pharmacology and experimental therapeutics · 2019Article
- Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos.Pharmaceuticals (Basel, Switzerland) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Norbuprenorphine is a major metabolite of buprenorphine and potent agonist of μ, δ, and κ opioid receptors. Compared with buprenorphine, norbuprenorphine causes minimal antinociception but greater respiratory depression. It is unknown whether the limited antinociception is caused by low efficacy or limited brain exposure. Norbuprenorphine is an in vitro substrate of the efflux transporter P-glycoprotein (Mdr1), but the role of P-glycoprotein in norbuprenorphine transport in vivo is unknown. This investigation tested the hypothesis that limited norbuprenorphine antinociception results from P-glycoprotein-mediated efflux and limited brain access. Human P-glycoprotein-mediated transport in vitro of buprenorphine, norbuprenorphine, and their respective glucuronide conjugates was assessed by using transfected cells. P-glycoprotein-mediated norbuprenorphine transport and consequences in vivo were assessed by using mdr1a(+/+) and mdr1a(-/-) mice. Antinociception was determined by hot-water tail-flick assay, and respiratory effects were determined by unrestrained whole-body plethysmography. Brain and plasma norbuprenorphine and norbuprenorphine-3-glucuronide were quantified by mass spectrometry. In vitro, the net P-glycoprotein-mediated efflux ratio for norbuprenorphine was nine, indicating significant efflux. In contrast, the efflux ratio for buprenorphine and the two glucuronide conjugates was unity, indicating absent transport. The norbuprenorphine brain/plasma concentration ratio was significantly greater in mdr1a(-/-) than mdr1a(+/+) mice. The magnitude and duration of norbuprenorphine antinociception were significantly increased in mdr1a(-/-) compared with mdr1a(+/+) mice, whereas the reduction in respiratory rate was similar. Results show that norbuprenorphine is an in vitro and in vivo substrate of P-glycoprotein. P-glycoprotein-mediated efflux influences brain access and antinociceptive, but not the respiratory, effects of norbuprenorphine.
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Registered trials
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.