Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats
Open accessAbstract
Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe and Brazil for treating attention deficit hyperactivity disorder (ADHD). It undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine. Following our previous work comparing lisdexamfetamine with d-amphetamine, the neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement. We employed pharmacologically equivalent doses of all compounds and those that spanned the therapeutically relevant and psychostimulant range. Lisdexamfetamine (0.5, 1.5, 4.5 mg/kg d-amphetamine base, per os (po)), methylphenidate (3, 10, 30 mg/kg base, po) and modafinil (100, 300, 600 mg/kg base, po) increased efflux of dopamine and noradrenaline in PFC, and dopamine in striatum. Only lisdexamfetamine increased 5-hydroxytryptamine (5-HT) efflux in PFC and striatum. Lisdexamfetamine had larger and more sustained effects on catecholaminergic neurotransmission than methylphenidate or modafinil. Linear correlations were observed between striatal dopamine efflux and locomotor activity for lisdexamfetamine and methylphenidate, but not modafinil. Regression slopes revealed greater increases in extracellular dopamine could be elicited without producing locomotor activation by lisdexamfetamine than methylphenidate. These results are cons…
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Due to its unique pharmacokinetics, lisdexamfetamine shows a lower reward property and a larger therapeutic window than d-amphetamine.
“Due to the unique pharmacokinetics, lisdexamfetamine shows a lower reward property and larger therapeutic window than d-amphetamine (21, 38).”
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“5 mg/kg produced the lasting increased locomotion from 60 to 180 min after administration (two-way ANOVA with one repeated measurement: main effect of time: F(11,38) = 25.”
BackgroundMethod
- Authors
- Rowley, H. L., Kulkarni, R. S., Gosden, J., Brammer, R. J., Hackett, D., & Heal, D. J.
- Affiliations
- RenaSci (United Kingdom) (GB)
- Shire (United Kingdom) (GB)
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2013-12-10
- Volume
- 28
- Issue
- 3
- Pages
- 254-269
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2007549798
- Cited by
- 65
- References
- 7
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 3
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Psychopharmacology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Shire
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- lisdexamfetamine, methylphenidate, modafinil, attention deficit hyperactivity disorder, dopamine efflux, noradrenaline efflux, serotonin efflux, prefrontal cortex, striatum, locomotor activity, catecholaminergic neurotransmission, psychostimulants, duration of action, stimulant side effects
- MeSH terms
- Lisdexamfetamine Dimesylate, Modafinil, Central Nervous System Stimulants, Animals, Behavior, Animal, Benzhydryl Compounds, Dextroamphetamine, Dose-Response Relationship, Drug, Male, Methylphenidate, Motor Activity, Rats, Sprague-Dawley, Prefrontal Cortex, Microdialysis, Rats
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