Evidence map›Paper›PMID 37348963›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2023

The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization.

Cassandra Small, Mary Hongying Cheng, Saron S Belay, Sarah L Bulloch, Brooke Zimmerman, Alexander Sorkin, Ethan R Block

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

Article in The Journal of pharmacology and experimental therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 42% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Nutrients · 2024
    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

7 authors at 2 institutions in 1 country.

Cassandra SmallScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Mary Hongying ChengScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Saron S BelayScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Sarah L BullochScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Brooke ZimmermanScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Alexander SorkinScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ethan R BlockScience Department, Chatham University, Pittsburgh, Pennsylvania (C.S., S.S.B., S.L.B., B.Z., E.R.B.) and Departments of Computational and Systems Biology (M.H.C.) and Cell Biology (A.S.), School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania eblock@chatham.edu.
University of Pittsburgh · USChatham University · US

Funding

Regulation of Dopamine Transporter by TraffickingR01DA014204 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALEXANDER D SORKIN · 2001 to 2026
$8.3M
Toward a Deeper Understanding of Allostery and Allotargeting by Computational ApproachesR01GM139297 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ivet Bahar · 2021 to 2026
$2.8M
NIDA NIH HHS R01 DA014204NIGMS NIH HHS R01 GM139297
6 · The paper itself

Abstract

The alkylamine stimulant 1,3-dimethylamylamine (DMAA) is used nonmedically as an appetite suppressant and exercise performance enhancer despite adverse cardiovascular effects that have limited its legal status. There is scant research describing the mechanism of action of DMAA, making it difficult to gauge risks or therapeutic potential. An important molecular target of structurally related phenethylamines, such as amphetamine, for regulating mood, cognition, movement, and the development of substance use disorder is the dopamine transporter, which limits the range and magnitude of dopamine signaling via reuptake from the extracellular space. The present studies were therefore initiated to characterize the effects of DMAA on dopamine transporter function. Specifically, we tested the hypothesis that DMAA exhibits substrate-like effects on dopamine transporter function and trafficking. In transport assays in human embryonic kidney cells, DMAA inhibited dopamine uptake by the human dopamine transporter in a competitive manner. Docking analysis and molecular dynamics simulations supported these findings, revealing that DMAA binds to the S1 substrate binding site and induces a conformational change from outward-facing open to outward-facing closed states, similar to the known substrates. Further supporting substrate-like effects of DMAA, the drug stimulated dopamine transporter endocytosis in a heterologous expression system via cocaine- and protein kinase A-sensitive mechanisms, mirroring findings with amphetamine. Together, these data indicate that DMAA elicits neurologic effects by binding to and regulating function of the dopamine transporter. Furthermore, pharmacologic distinctions from amphetamine reveal structural determinants for regulating transporter conformation and add mechanistic insight for the regulation of dopamine transporter endocytosis. SIGNIFICANCE STATEMENT: The alkylamine stimulant 1,3-dimethylamylamine (DMAA) is used as an appetite suppressant and athletic performance enhancer and is structurally similar to amphetamine, but there is scant research describing its mechanism of action. Characterizing the effects of DMAA on dopamine transporter function supports evaluation of potential risks and therapeutic potential while also revealing mechanistic details of dynamic transporter-substrate interactions.

Indexed as

Appetite DepressantsCocaineAminesAmphetamineCentral Nervous System AgentsDopamineDopamine Plasma Membrane Transport ProteinsHumans1,3-dimethylamylamineAminesAmphetamineAppetite DepressantsCentral Nervous System AgentsCocaineDopamineDopamine Plasma Membrane Transport Proteins

Identifiers

PMID37348963
PMCPMC10353075
OpenAlexW4381682970

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.