Cited by 885Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate

Volkow, Nora D., Wang, Gene.-Jack, Fowler, Joanna S., Gatley, Samuel J., Logan, Jean, Ding, Yu-Shin, Hitzemann, Robert, Pappas, Naomi·1998·American Journal of Psychiatry

Abstract

OBJECTIVE: The therapeutic effects of methylphenidate in the treatment of attention deficit disorder have been attributed to its ability to increase the synaptic concentration of dopamine by blocking the dopamine transporters. However, the levels of dopamine transporter blockade achieved by therapeutic doses of methylphenidate are not known. This study measured, for the first time, dopamine transporter occupancy by orally administered methylphenidate in the human brain and its rate of uptake in the brain. METHOD: Positron emission tomography (PET) and [11C]cocaine were used to estimate dopamine transporter occupancies after different doses of oral methylphenidate in seven normal subjects (mean age=24 years, SD=7). In addition, the pharmacokinetics of oral methylphenidate were measured in the baboon brain through use of PET and [11C]methylphenidate administered through an orogastric tube. RESULTS: At 120 minutes after administration, oral methylphenidate produced a dose-dependent blockade of dopamine transporter; means=12% (SD= 4%) for 5 mg, 40% (SD=12%) for 10 mg, 54% (SD=5%) for 20 mg, 72% (SD=3%) for 40 mg, and 74% (SD=2%) for 60 mg. The estimated dose of oral methylphenidate required to block 50% of the dopamine transporter corresponded to 0.25 mg/kg. Oral methylphenidate did not reach peak concentration in brain until 60 minutes after its administration. CONCLUSIONS: Oral methylphenidate is very effective in blocking dopamine transporters, and at the weight-adjusted doses used therapeutically (0.3 to 0.6 mg/kg), it is likely to occupy more than 50% of the dopamine transporters. The time to reach peak brain uptake for oral methylphenidate in brain corresponds well with the reported time course to reach peak behavioral effects.

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Crossref · 10.1176/ajp.155.10.1325

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Authors
Volkow, N. D., Wang, G.-J., Fowler, J. S., Gatley, S. J., Logan, J., Ding, Y.-S., Hitzemann, R., & Pappas, N.
Affiliations
Brookhaven National Laboratory (US)
Venue
American Journal of Psychiatry
Published
1998-10-01
Volume
155
Issue
10
Pages
1325-1331
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
OpenAlex
W1977634040
Cited by
885
References
36
Citations by year
2026: 9 · 2025: 13 · 2024: 19 · 2023: 7 · 2022: 15 · 2021: 12 · 2020: 26 · 2019: 20 · 2018: 14 · 2017: 38 · 2016: 35 · 2015: 28 · 2014: 46 · 2013: 42 · 2012: 48
FWCI
18.95
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01da009490-08)
  • National Institute on Drug Abuse (DA-09490)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
methylphenidate, attention deficit disorder, oral administration, pharmacokinetics, dose-response relationship, baboon brain
MeSH terms
Administration, Oral, Adult, Animals, Attention Deficit Disorder with Hyperactivity, Brain, Brain Chemistry, Carbon Radioisotopes, Carrier Proteins, Cocaine, Dopamine, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Membrane Glycoproteins, Methylphenidate, Nerve Tissue Proteins, Papio, Tomography, Emission-Computed, Dopamine Antagonists, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins

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