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Pharmacokinetic and pharmacodynamic properties of stimulants: implications for the design of new treatments for ADHD
Abstract
In the USA, the stimulant drug methylphenidate (MPH) is used to treat a large number (2 million or more per year) of children with Attention Deficit Hyperactivity Disorder (ADHD). Although the US FDA approved MPH in the 1960s, the pharmacokinetic (PK) properties of serum concentrations of MPH in children with ADHD were not described until the 1980s, and then in only a few cases. Recently, information from drug development programs have increased our knowledge about the serum PK and some pharmacodynamic (PD) characteristics of MPH in ADHD children, and studies based on positron emission tomograpy (PET) in adult volunteers have provided new knowledge about the PK properties of MPH at the primary site of action in the brain. We will review these two topics and use this new information to evaluate the mechanisms of action of MPH.
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“PET imaging studies have shown that therapeutic doses of stimulant medications engage DA receptors in striatum (Swanson and Volkow, 2002), consistent with the small but significant increases in DA release measured in rodent striatum (Berridge et al., 2006).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Swanson and Volkow, 2002
In the citing paper
“Decreasing the rate of absorption and the actions of an addictive drug on its targets reduce its rewarding effects and may aid in quitting [247, 248].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [248]
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References 51 · Cited by 173
Metadata
- Authors
- Swanson, J. M., & Volkow, N. D.
- Affiliations
- University of California, Irvine (US)
- Brookhaven National Laboratory (US)
- Corresponding author
- Swanson, J.M
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 130
- Issue
- 1-2
- Pages
- 73-78
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2044451720
- Cited by
- 173
- References
- 51
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 12 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 9
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- methylphenidate, attention deficit hyperactivity disorder, pharmacokinetics, pharmacodynamics, children, brain drug distribution, positron emission tomography, mechanism of action, stimulants, ADHD treatment
- MeSH terms
- Central Nervous System Stimulants, Animals, Attention Deficit Disorder with Hyperactivity, Child, Humans, Membrane Glycoproteins, Methylphenidate, Nerve Tissue Proteins, Tomography, Emission-Computed, Membrane Transport Proteins, Membrane Transport Modulators, Dopamine Plasma Membrane Transport Proteins
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