ArticleACS chemical neuroscience2017
The Isomeric Preference of an Atypical Dopamine Transporter Inhibitor Contributes to Its Selection of the Transporter Conformation.
Article in ACS chemical neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- RDS-04-010: a novel atypical DAT inhibitor that inhibits cocaine taking and seeking and itself has low abuse potential in experimental animals.Translational psychiatry · 2025Article
- Article
- Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling.Advances in neurobiology · 2025Review
- The Structural Basis of the Activity Cliff in Modafinil-Based Dopamine Transporter Inhibitors.Biomolecules · 2024Article
- Incorporation of Multiple βACS central science · 2024Article
- Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.The European journal of neuroscience · 2024Article
- Series of (([1,1'-Biphenyl]-2-yl)methyl)sulfinylalkyl Alicyclic Amines as Novel and High Affinity Atypical Dopamine Transporter Inhibitors with Reduced hERG Activity.ACS pharmacology & translational science · 2024Article
- Modifications to 1-(4-(2-Bis(4-fluorophenyl)methyl)sulfinyl)alkyl Alicyclic Amines That Improve Metabolic Stability and Retain an Atypical DAT Inhibitor Profile.Journal of medicinal chemistry · 2024Article
- Modafinil, an atypical CNS stimulant?Advances in pharmacology (San Diego, Calif.) · 2024Article
- Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Interactions of calmodulin kinase II with the dopamine transporter facilitate cocaine-induced enhancement of evoked dopamine release.Translational psychiatry · 2023Article
- Biodiscoveries within the Australian plant genus Eremophila based on international and interdisciplinary collaboration: results and perspectives on outstanding ethical dilemmas.The Plant journal : for cell and molecular biology · 2022Review
- Evaluation of Urea-Based Inhibitors of the Dopamine Transporter Using the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.ACS chemical neuroscience · 2022Article
- Toward Reducing hERG Affinities for DAT Inhibitors with a Combined Machine Learning and Molecular Modeling Approach.Journal of chemical information and modeling · 2021Article
- Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter.Biomedicines · 2021Article
- Chemogenetic Manipulation of Dopamine Neurons Dictates Cocaine Potency at Distal Dopamine Transporters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Structure-Activity Relationships for a Series of (Bis(4-fluorophenyl)methyl)sulfinyl Alkyl Alicyclic Amines at the Dopamine Transporter: Functionalizing the Terminal Nitrogen Affects Affinity, Selectivity, and Metabolic Stability.Journal of medicinal chemistry · 2020Article
- The Glu102 mutation disrupts higher-order oligomerization of the sigma 1 receptor.Computational and structural biotechnology journal · 2020Article
- Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics.Neuropharmacology · 2019Article
- Identification of a Novel Allosteric Modulator of the Human Dopamine Transporter.ACS chemical neuroscience · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT) by trapping the protein in an outward-open conformation, whereas atypical DAT inhibitors such as benztropine have low abuse liability and prefer less outward-open conformations. Here, we use a spectrum of computational modeling and simulation approaches to obtain the underlying molecular mechanism in atomistic detail. Interestingly, our quantum mechanical calculations and molecular dynamics (MD) simulations suggest that a benztropine derivative JHW007 prefers a different stereoisomeric conformation of tropane in binding to DAT compared to that of a cocaine derivative, CFT. To further investigate the different inhibition mechanisms of DAT, we carried out MD simulations in combination with Markov state modeling analysis of wild-type and Y156F DAT in the absence of any ligand or the presence of CFT or JHW007. Our results indicate that the Y156F mutation and CFT shift the conformational equilibrium toward an outward-open conformation, whereas JHW007 prefers an inward-occluded conformation. Our findings reveal the mechanistic details of DAT inhibition by JHW007 at the atomistic level, which provide clues for rational design of atypical inhibitors.
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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.