Cited by 580Neurotransmitter Receptor Influence on BehaviorAttention Deficit Hyperactivity DisorderPharmacogenetics and Drug Metabolism

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Is Methylphenidate Like Cocaine?: Studies on Their Pharmacokinetics and Distribution in the Human Brain

Volkow, Nora D.·1995·Archives of General Psychiatry

DOI 10.1001/archpsyc.1995.03950180042006

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Abstract

BACKGROUND: The purposes of this study were to investigate the pharmacokinetics of methylphenidate hydrochloride (Ritalin) in the human brain, to compare them with those of cocaine, and to evaluate whether cocaine and methylphenidate compete for the same binding sites. METHODS: We used positron emission tomography to measure the temporal and spatial distribution of carbon 11 (11C)-labeled methylphenidate. These results were compared with those obtained previously for [11C]cocaine. Eight healthy male subjects, 20 to 51 years of age, were scanned with [11C]methylphenidate. Three were tested twice to assess test-retest variability, four were tested at baseline and after administration of methylphenidate, and one was tested with [11C]methylphenidate and [11C]cocaine. Two baboons were scanned to evaluate whether there was competition between cocaine and methylphenidate for the same binding sites in the brain. RESULTS: The uptake of [11C]methylphenidate in the brain was high (mean +/- SD, 7.5% +/- 1.5%), and the maximal concentration occurred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [11C]methylphenidate, was identical to that of [11C]cocaine and they competed with each other for the same binding sites, these two drugs differed markedly in their pharmacokinetics. Clearance of [11C]methylphenidate from striatum (90 minutes) was significantly slower than that of [11C]cocaine (20 minutes). For both drugs, their fast uptake in striatum paralleled the experience of the "high." For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high paralleled its fast rate of clearance from the brain. CONCLUSION: We speculate that because the experience of the high is associated with the fast uptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in promoting its frequent self-administration.

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Authors: Volkow, N. D.
Affiliations: Brookhaven National Laboratory (US)
Corresponding author: Volkow, Nora D.
ORCID: Volkow, Nora D.
Venue: Archives of General Psychiatry
Publisher: American Medical Association (AMA)
Published: 1995-06-01
Volume: 52
Issue: 6
Pages: 456
ISSN: 0003-990X (ISSN-L)
DOI: 10.1001/archpsyc.1995.03950180042006
OpenAlex: W2116795024
Cited by: 575
References: 47
Citations by year: 2026: 2 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 16 · 2015: 20 · 2014: 21 · 2013: 22 · 2012: 33
FWCI: 5.34
Type: journal article
Language: en
Open access: closed
Locations: Archives of General Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01ns015638-15)
National Institute on Drug Abuse (5RO1-DA06891, R01DA006891)
National Institute of Neurological Disorders and Stroke (NS15638)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: methylphenidate, cocaine, brain pharmacokinetics, striatum, binding site competition, drug clearance, self-administration, positron emission tomography
MeSH terms: Adult, Animals, Brain, Carbon Radioisotopes, Cerebellum, Cocaine, Corpus Striatum, Half-Life, Humans, Male, Methylphenidate, Middle Aged, Papio, Self Medication, Time Factors, Tissue Distribution, Tomography, Emission-Computed, Substance-Related Disorders

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Is Methylphenidate Like Cocaine?: Studies on Their Pharmacokinetics and Distribution in the Human Brain

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