ArticlePharmaceutical research2000
Morphine antinociception is enhanced in mdr1a gene-deficient mice.
Article in Pharmaceutical research, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 101 citations in OpenAlex.
- The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone.British journal of clinical pharmacology · 2004Trial
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway.Scientific reports · 2024Article
- Essential role of P-glycoprotein in the mechanism of action of oliceridine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Morphine Accumulates in the Retina Following Chronic Systemic Administration.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats.Pharmaceutics · 2021Article
- Nonclinical safety assessment of PF614: A novel TAAP prodrug of oxycodone for chronic pain indication.Regulatory toxicology and pharmacology : RTP · 2019Article
- Morphine: double-faced roles in the regulation of tumor development.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain.Current neuropharmacology · 2017Review
- Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level.Renal failure · 2017Article
- Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts.Scientific reports · 2016Article
- The ontogeny of P-glycoprotein in the developing human blood-brain barrier: implication for opioid toxicity in neonates.Pediatric research · 2015Article
- Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions.Pharmaceutical research · 2015Review
- Liposomal conjugates for drug delivery to the central nervous system.Pharmaceutics · 2015Article
- Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression.BioMed research international · 2015Article
- Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties.Psychopharmacology · 2014Article
- Cyclosporine-inhibitable blood-brain barrier drug transport influences clinical morphine pharmacodynamics.Anesthesiology · 2013Article
- The role of multidrug resistance-associated protein in the blood-brain barrier and opioid analgesia.Synapse (New York, N.Y.) · 2013Article
- Mu opioids and their receptors: evolution of a concept.Pharmacological reviews · 2013Review
- The role of morphine in animal models of human cancer: does morphine promote or inhibit the tumor growth?BioMed research international · 2013Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePrevious studies have suggested that P-glycoprotein (P-gp) modulates opioid antinociception for selected mu-and delta-agonists. This study was undertaken to assess morphine antinociception in mice lacking the mdr1a gene for expression of P-gp in the CNS.
methodsMorphine (n = 4-5/group) was administered as a single s.c. dose to mdr1a(-/-) mice (3-5 mg/kg) or wild-type FVB controls (8-10 mg/kg). Tail-flick response to radiant heat, expressed as percent of maximum response (%MPR), was used to determine the antinociceptive effect of morphine. Concentrations in serum, brain tissue, and spinal cord samples obtained immediately after the tail-flick test were determined by HPLC with fluorescence detection. Parallel experiments with R(+)-verapamil, a chemical inhibitor of P-gp, also were performed to further investigate the effect of P-gp on morphine-associated antinociception.
resultsMorphine-associated antinociception was increased significantly in the mdr1a(-/-) mice. The ED50 for morphine was > 2-fold lower in mdr1a(-/-) (3.8+/-0.2 mg/kg) compared to FVB (8.8+/-0.2 mg/kg) mice. However, the EC50 derived from the brain tissue was similar between the two mouse strains (295 ng/g vs. 371 ng/g). Pretreatment with R(+)-verapamil produced changes similar to those observed in gene-deficient mice. P-gp does not appear to affect morphine distribution between spinal cord and blood, as the spinal cord:serum morphine concentration ratio was similar between gene-deficient and wild-type mice (0.47+/-0.03 vs. 0.56+/-0.04, p>0.05).
conclusionsThe results of this study are consistent with the hypothesis that P-gp attenuates the antinociceptive action of morphine by limiting the brain:blood partitioning of the opioid.
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