New Insights into the Mechanism of Action of Amphetamines
Abstract
Amphetamine is a psychostimulant commonly used to treat several disorders, including attention deficit, narcolepsy, and obesity. Plasmalemmal and vesicular monoamine transporters, such as the neuronal dopamine transporter and the vesicular monoamine transporter-2, are two of its principal targets. This review focuses on new insights, obtained from both in vivo and in vitro studies, into the molecular mechanisms whereby amphetamine, and the closely related compounds methamphetamine and methylenedioxymethamphetamine, cause monoamine, and particularly dopamine, release. These mechanisms include amphetamine-induced exchange diffusion, reverse transport, and channel-like transport phenomena as well as the weak base properties of amphetamine. Additionally, amphetamine analogs may affect monoamine transporters through phosphorylation, transporter trafficking, and the production of reactive oxygen and nitrogen species. All of these mechanisms have potential implications for both amphetamine- and methamphetamine-induced neurotoxicity, as well as dopaminergic neurodegenerative diseases.
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Amphetamine increases synaptic levels of monoamines (dopamine, noradrenaline and serotonin) by increasing their release through a reversal of the monoamine transporters, primarily the catecholamine transporters.
“AMP increases the synaptic levels of monoamines (dopamine, noradrenaline and serotonin) by increasing their release through a reversal of the monoamine transporters, primarily the catecholamine transporters (see Fleckenstein et al., 2007; Hutson et al., 2014, for review; Kuczenski et al., 1995; Sulzer et al., 2005).”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Fleckenstein et al., 2007
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“AMP is a prototype psychostimulant (Berman et al., 2009; Fleckenstein et al., 2007; Hutson et al., 2014), used for the treatment of attention deficit hyperactivity disorder (ADHD) (Castells et al., 2018; Easton et al., 2007), narcolepsy (Turner, 2019), and obesity (Harris et al., 1947).”
Background
- Authors
- Fleckenstein, A. E., Volz, T. J., Riddle, E. L., Gibb, J. W., & Hanson, G. R.
- Affiliations
- University of Utah (US)
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2007-02-01
- Volume
- 47
- Issue
- 1
- Pages
- 681-698
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W2131622291
- Cited by
- 731
- References
- 3
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 22 · 2023: 26 · 2022: 30 · 2021: 45 · 2020: 65 · 2019: 30 · 2018: 45 · 2017: 32 · 2016: 45 · 2015: 54 · 2014: 52 · 2013: 43 · 2012: 55
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (R01DA000869, DA013367, K05DA000378, P01DA013367, DA 011389, K02DA019447, DA 004222, DA 000378, DA019447, DA 000869, R01DA004222)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- amphetamine, methamphetamine, MDMA, psychostimulants, dopamine release, dopamine transporter, vesicular monoamine transporter 2, monoamine transporters, exchange diffusion, reverse transport, transporter trafficking, reactive oxygen species, reactive nitrogen species, neurotoxicity, attention deficit disorder, narcolepsy, obesity
- MeSH terms
- Amphetamines, Central Nervous System Stimulants, Animals, Humans, Methamphetamine, Neurotoxicity Syndromes, Dopamine Plasma Membrane Transport Proteins, Vesicular Monoamine Transport Proteins
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