ArticleJournal of pharmaceutical sciences2017
Insights Into the Molecular Mechanism of Triptan Transport by P-glycoprotein.
Article in Journal of pharmaceutical sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 36 citations in OpenAlex.
- Regional distribution of unbound eletriptan and sumatriptan in the CNS and PNS in rats: implications for a potential central action.The journal of headache and pain · 2024Article
- The putative proton-coupled organic cation antiporter is involved in uptake of triptans into human brain capillary endothelial cells.Fluids and barriers of the CNS · 2024Article
- Utilizing surface plasmon resonance as a novel method for monitoringFrontiers in biophysics · 2024Article
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- Four Decades of Cytochrome P450 2B Research: From Protein Adducts to Protein Structures and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- 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
- Structure-based alteration of tryptophan residues of the multidrug transporter CmABCB1 to assess substrate binding using fluorescence spectroscopy.Protein science : a publication of the Protein Society · 2022Article
- Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor That Induces CYP1A1 in Hepatic and Intestinal Cells.International journal of molecular sciences · 2020Article
- The effects of anthracycline drugs on the conformational distribution of mouse P-glycoprotein explains their transport rate differences.Biochemical pharmacology · 2020Article
- The conformation and dynamics of P-glycoprotein in a lipid bilayer investigated by atomic force microscopy.Biochemical pharmacology · 2018Article
- A Conformationally Gated Model of Methadone and Loperamide Transport by P-Glycoprotein.Journal of pharmaceutical sciences · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The P-glycoprotein (Pgp) transporter reduces the penetration of a chemically diverse range of neurotherapeutics at the blood-brain barrier, but the molecular features of drugs and drug-Pgp interactions that drive transport remain to be clarified. In particular, the triptan neurotherapeutics, eletriptan (ETT) and sumatriptan (STT), were identified to have a >10-fold difference in transport rates despite being from the same drug class. Consistent with these transport differences, ETT activated Pgp-mediated ATP hydrolysis ∼2-fold, whereas STT slightly inhibited Pgp-mediated ATP hydrolysis by ∼10%. The interactions between them were also noncompetitive, suggesting that they occupy different binding sites on the transporter. Despite these differences, protein fluorescence spectroscopy revealed that the drugs have similar affinity to the transporter. NMR with Pgp and the drugs showed that they have distinct interactions with the transporter. Tertiary conformational changes probed by acrylamide quenching of Pgp tryptophan fluorescence with the drugs and a nonhydrolyzable ATP analog implied that the STT-bound Pgp must undergo larger conformational changes to hydrolyze ATP than ETT-bound Pgp. These results and previous transport studies were used to build a conformationally driven model for triptan transport with Pgp where STT presents a higher conformational barrier for ATP hydrolysis and transport than ETT.
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Registered trials
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