Evidence map›Paper›PMID 26285765›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2015

Potent and Selective Inhibition of Plasma Membrane Monoamine Transporter by HIV Protease Inhibitors.

Haichuan Duan, Tao Hu, Robert S Foti, Yongmei Pan, Peter W Swaan, Joanne Wang

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 51 citations in OpenAlex.

  1. Signaling by intracellular βCell reports · 2025
    Article
  2. Use of a Double-Transfected System to Predict hOCT2/hMATE1-Mediated Renal Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2024
    Article
  3. Review
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  11. MPPInternational journal of molecular sciences · 2022
    Article
  12. Review
  13. General Overview of Organic Cation Transporters in Brain.Handbook of experimental pharmacology · 2021
    Article
  14. Brain Plasma Membrane Monoamine Transporter in Health and Disease.Handbook of experimental pharmacology · 2021
    Article
  15. Article
  16. Article
  17. HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Haichuan DuanDepartment of Pharmaceutics, University of Washington, Seattle, Washington (H.D., T.H., J.W.); Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Seattle, Washington (R.S.F.); and Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland (Y.P., P.W.S.).
Tao HuDepartment of Pharmaceutics, University of Washington, Seattle, Washington (H.D., T.H., J.W.); Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Seattle, Washington (R.S.F.); and Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland (Y.P., P.W.S.).
Robert S FotiDepartment of Pharmaceutics, University of Washington, Seattle, Washington (H.D., T.H., J.W.); Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Seattle, Washington (R.S.F.); and Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland (Y.P., P.W.S.).
Yongmei PanDepartment of Pharmaceutics, University of Washington, Seattle, Washington (H.D., T.H., J.W.); Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Seattle, Washington (R.S.F.); and Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland (Y.P., P.W.S.).
Peter W SwaanDepartment of Pharmaceutics, University of Washington, Seattle, Washington (H.D., T.H., J.W.); Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Seattle, Washington (R.S.F.); and Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland (Y.P., P.W.S.).
Joanne WangDepartment of Pharmaceutics, University of Washington, Seattle, Washington (H.D., T.H., J.W.); Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Seattle, Washington (R.S.F.); and Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland (Y.P., P.W.S.) jowang@u.washington.edu.
University of Maryland, Baltimore · USUniversity of Washington · USAmgen (United States) · US

Funding

The plasma membrane monoamine transporter (PMAT): expression and role in mIBG disposition in neuroblastomaR01GM066233 · NIGMS · UNIVERSITY OF WASHINGTON · PI WANG, JOANNE · 2002 to 2020
$5.1M
NIGMS NIH HHS GM066233NIGMS NIH HHS R01 GM066233
6 · The paper itself

Abstract

Plasma membrane monoamine transporter (PMAT) is a major uptake-2 monoamine transporter that shares extensive substrate and inhibitor overlap with organic cation transporters 1-3 (OCT1-3). Currently, there are no PMAT-specific inhibitors available that can be used in in vitro and in vivo studies to differentiate between PMAT and OCT activities. In this study, we showed that IDT307 (4-(4-(dimethylamino)phenyl)-1-methylpyridinium iodide), a fluorescent analog of 1-methyl-4-phenylpyridinium (MPP+), is a transportable substrate for PMAT and that IDT307-based fluorescence assay can be used to rapidly identify and characterize PMAT inhibitors. Using the fluorescent substrate-based assays, we analyzed the interactions of eight human immunodeficiency virus (HIV) protease inhibitors (PIs) with human PMAT and OCT1-3 in human embryonic kidney 293 (HEK293) cells stably transfected with individual transporters. Our data revealed that PMAT and OCTs exhibit distinct sensitivity and inhibition patterns toward HIV PIs. PMAT is most sensitive to PI inhibition whereas OCT2 and OCT3 are resistant. OCT1 showed an intermediate sensitivity and a distinct inhibition profile from PMAT. Importantly, lopinavir is a potent PMAT inhibitor and exhibited >120 fold selectivity toward PMAT (IC₅₀ = 1.4 ± 0.2 µM) over OCT1 (IC₅₀ = 174 ± 40 µM). Lopinavir has no inhibitory effect on OCT2 or OCT3 at maximal tested concentrations. Lopinavir also exhibited no or much weaker interactions with uptake-1 monoamine transporters. Together, our results reveal that PMAT and OCTs have distinct specificity exemplified by their differential interaction with HIV PIs. Further, we demonstrate that lopinavir can be used as a selective PMAT inhibitor to differentiate PMAT-mediated monoamine and organic cation transport from those mediated by OCT1-3.

Indexed as

Biological TransportDose-Response Relationship, DrugEquilibrative Nucleoside Transport ProteinsHEK293 CellsHIV Protease InhibitorsHumansOrganic Cation Transporter 1Organic Cation Transporter 2Organic Cation Transporter 3Organic Cation Transport ProteinsEquilibrative Nucleoside Transport ProteinsHIV Protease InhibitorsOrganic Cation Transporter 1Organic Cation Transporter 2Organic Cation Transporter 3Organic Cation Transport ProteinsSLC22A2 protein, humanSLC29A4 protein, human

Identifiers

PMID26285765
PMCPMC4613949
OpenAlexW1786595753

What OpenQuestion holds

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Registered trials

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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.