ArticleBiological psychiatry2012
R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse.
Article in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Sleep disorders in Parkinson's disease: evaluating pharmacological treatments through systematic review and meta-analysis.BMC neurology · 2025Pooled it
- Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Efficacité et innocuité du modafinil pour le traitement des troubles liés à l'usage de stimulants de type amphétamine : revue systématique et méta-analyse d'essais randomisés contrôlés par placebo.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2024Pooled it
- Trial
- Modafinil and sleep architecture in an inpatient-outpatient treatment study of cocaine dependence.Drug and alcohol dependence · 2016Trial
- A Series of Aryl-Substituted-(biphenyl)methyl-sulfinylmethylthiazoles as Novel and Atypical Dopamine Transporter Inhibitors.Journal of medicinal chemistry · 2026Article
- Narcolepsy: Pathophysiology, Diagnosis, Management, and Future Directions, a Narrative Review.Brain and behavior · 2025Review
- Repurposing drugs for the human dopamine transporter through WHALES descriptors-based virtual screening and bioactivity evaluation.Journal of pharmaceutical analysis · 2025Article
- 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
- Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling.Advances in neurobiology · 2025Review
- Novel Ways of Targeting the Dopamine Transporter.Advances in neurobiology · 2025Review
- Functional neuroanatomy of dopaminergic arousal systems: implications for the wake-promoting effect of psychostimulants, with particular reference to modafinil.Frontiers in neuroanatomy · 2025Review
- Contrasting the reinforcing effects of the novel dopamine transport inhibitors JJC8-088 and JJC8-091 in monkeys: Potential translation to medication assisted treatment.The Journal of pharmacology and experimental therapeutics · 2025Article
- Article
- Expanding the toolbox of Baeyer-Villiger and flavin monooxygenase biocatalysts for the enantiodivergent green synthesis of sulfoxides.Green chemistry : an international journal and green chemistry resource : GC · 2024Article
- The Structural Basis of the Activity Cliff in Modafinil-Based Dopamine Transporter Inhibitors.Biomolecules · 2024Article
- Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.The European journal of neuroscience · 2024Article
- Article
- 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
- Armodafinil as a Potential Pharmacological Treatment for Attention Deficit Hyperactivity Disorder in Adults: A Review.Current neuropharmacology · 2024Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
background(±)-Modafinil has piqued interest as a treatment for attention-deficit/hyperactivity disorder and stimulant dependence. The R-enantiomer of modafinil might have unique pharmacological properties that should be further investigated.
methods(±)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of [(3)H] dopamine (DA) uptake and [(3)H]WIN 35428 binding in human dopamine transporter (DAT) wild-type and mutants with altered conformational equilibria. Data were compared with cocaine and the atypical DA uptake inhibitor, JHW 007. R- and S-modafinil were also evaluated in microdialysis studies in the mouse nucleus accumbens shell and in a cocaine discrimination procedure.
results(±)-, R-, and S-modafinil bind to the DAT and inhibit DA uptake less potently than cocaine, with R-modafinil having approximately threefold higher affinity than its S-enantiomer. Molecular docking studies revealed subtle differences in binding modes for the enantiomers. R-modafinil was significantly less potent in the DAT Y156F mutant compared with wild-type DAT, whereas S-modafinil was affected less. Studies with the Y335A DAT mutant showed that the R- and S-enantiomers tolerated the inward-facing conformation better than cocaine, which was further supported by [2-(trimethylammonium)ethyl]-methanethiosulfonate reactivity on the DAT E2C I159C. Microdialysis studies demonstrated that both R- and S-modafinil produced increases in extracellular DA concentrations in the nucleus accumbens shell less efficaciously than cocaine and with a longer duration of action. Both enantiomers fully substituted in mice trained to discriminate cocaine from saline.
conclusionsR-modafinil displays an in vitro profile different from cocaine. Future trials with R-modafinil as a substitute therapy with the potential benefit of cognitive enhancement for psychostimulant addiction are warranted.
Indexed as
Identifiers
What OpenQuestion holds
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.