Trial reportBiological psychiatry2010
Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo.
Trial report in Biological psychiatry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 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
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 237 citations in OpenAlex.
- Effects of stimulants on brain function in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.Biological psychiatry · 2014Pooled it
- Areas of the brain modulated by single-dose methylphenidate treatment in youth with ADHD during task-based fMRI: a systematic review.Harvard review of psychiatryPooled it
- Uncovering lipid biomarkers linked to methylphenidate efficacy in treating apathy in Alzheimer's disease: insights from the ADMET 2 trial.Alzheimer's research & therapy · 2026Trial
- Methylphenidate (Ritalin) does not improve exam performance in an experimental setting.Psychopharmacology · 2026Trial
- Catecholaminergic Modulation of Semantic Processing in Sentence Comprehension.Cerebral cortex (New York, N.Y. : 1991) · 2020Trial
- Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.Psychopharmacology · 2020Trial
- Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects.Psychopharmacology · 2018Trial
- Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.The international journal of neuropsychopharmacology · 2017Trial
- Central noradrenaline transporter availability in highly obese, non-depressed individuals.European journal of nuclear medicine and molecular imaging · 2017Trial
- Systemic inflammation enhances stimulant-induced striatal dopamine elevation.Translational psychiatry · 2017Trial
- Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.Psychopharmacology · 2017Trial
- Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study.Psychopharmacology · 2016Trial
- Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Trial
- Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Trial
- Waiting Impulsivity: The Influence of Acute Methylphenidate and Feedback.The international journal of neuropsychopharmacology · 2015Trial
- Sustained-release methylphenidate in methamphetamine dependence treatment: a double-blind and placebo-controlled trial.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2015Trial
- Shared and drug-specific effects of atomoxetine and methylphenidate on inhibitory brain dysfunction in medication-naive ADHD boys.Cerebral cortex (New York, N.Y. : 1991) · 2014Trial
- Distributed effects of methylphenidate on the network structure of the resting brain: a connectomic pattern classification analysis.NeuroImage · 2013Trial
- Effects of methylphenidate on resting-state functional connectivity of the mesocorticolimbic dopamine pathways in cocaine addiction.JAMA psychiatry · 2013Trial
- Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers.Psychopharmacology · 2012Trial
58 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAttention-deficit/hyperactivity disorder is a psychiatric disorder that starts in childhood. The mechanism of action of methylphenidate, the most common treatment for attention deficit hyperactivity disorder, is unclear. In vitro, the affinity of methylphenidate for the norepinephrine transporter (NET) is higher than that for the dopamine transporter (DAT). The goal of this study was to use positron emission tomography to measure the occupancy of brain norepinephrine transporter by methylphenidate in vivo in humans.
methodsWe used (S,S)-[¹¹C] methylreboxetine ([¹¹C]MRB) to determine the effective dose 50 (ED₅₀) of methylphenidate for NET. In a within-subject design, healthy subjects (n = 11) received oral, single-blind placebo and 2.5, 10, and 40 mg of methylphenidate 75 min before [¹¹C]MRB injection. Dynamic positron emission tomography imaging was performed for 2 hours with the High Resolution Research Tomograph. The multilinear reference tissue model with occipital cortex as the reference region was used to estimate binding potential non-displaceable (BP(ND)) in the thalamus and other NET-rich regions.
resultsBP(ND) was reduced by methylphenidate in a dose-dependent manner in thalamus and other NET-rich regions. The global ED₅₀ was estimated to be .14 mg/kg; therefore, the average clinical maintenance dose of methylphenidate (.35-.55 mg/kg) produces 70% to 80% occupancy of NET.
conclusionsFor the first time in humans, we demonstrate that oral methylphenidate significantly occupies NET at clinically relevant doses. The ED₅₀ is lower than that for DAT (.25 mg/kg), suggesting the potential relevance of NET inhibition in the therapeutic effects of methylphenidate in attention-deficit/hyperactivity disorder.
Indexed as
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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.