Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study
Open accessAbstract
The novel d-amphetamine prodrug lisdexamfetamine is applied to treat attention-deficit/hyperactivity disorder (ADHD). d-Amphetamine releases dopamine and norepinephrine and stimulates the hypothalamic-pituitary-adrenal (HPA) axis, which may contribute to its reinforcing effects and risk of abuse. However, no data is currently available on the effects of lisdexamfetamine on circulating steroids. This randomized, double-blind, placebo-controlled, cross-over study evaluated the effects of equimolar doses of d-amphetamine (40 mg) and lisdexamfetamine (100 mg) and placebo on circulating steroids in 24 healthy subjects. Plasma steroid and d-amphetamine levels were determined up to 24 h. Delayed increase and peak levels of plasma d-amphetamine concentrations were observed following lisdexamfetamine treatment compared with d-amphetamine administration, however the maximal concentrations and total exposure (area under the curve [AUC]) were similar. Lisdexamfetamine and d-amphetamine significantly enhanced plasma levels of adrenocorticotropic hormone, glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol), androgens (dehydroepiandrosterone, dehydroepiandrosterone sulfate, and Δ4-androstene-3,17-dione [androstenedione]), and progesterone (only in men) compared with placebo. Steroid concentration-time curves were shifted to later time points due to a non-significantly later onset following lisdexamfetamine administration than after d-ampheta…
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LDX modulates seven human protein targets: it activates TAAR1 and inhibits SLC18A2, DAT, NET, SERT, MAOA, and MAOB.
“LDX has been reported to modulate with pharmacological action of seven human protein targets (Table 2). On the one hand, it acts as activator of TAAR1. On the other hand, six protein targets are inhibited by LDX: synaptic vesicular amine transporter (SLC18A2), DAT (SLC6A3), NET (SLC6A2), SERT (SLC6A4) and amine oxidase [flavin-containing] (MAO) A and B [153–157].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [157]
MPH and LDX have similar targets and act in the same way: both promote the inhibition of DAT and NET.
“MPH and LDH have similar targets and act in the same way: both promote the inhibition of DAT and NET [153, 156, 157].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [157]
All of these targets are involved in presynaptic signalling, and LDX therefore has a role in regulating three main NT pathways: DA, NE and serotonin.
“All of these targets are involved in the presynaptic signalling, and LDX therefore has a role in regulating three main NT pathways: DA, NE and serotonin.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [157]
LDX inhibits DAT and NET transporters leading to an increase in DA and NE levels in the synaptic cleft.
“LDX inhibits DAT and NET transporters leading to an increase in DA and NE levels in the synaptic cleft [153, 156, 157].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [157]
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“After oral 63 administration, the conversion of lisdexamfetamine to D-amphetamine is thought to occur 64 gradually in the circulation [6], resulting in a prolonged pharmacokinetic profile with a low peak 65 but sustained plasma amphetamine concentrations [7].”
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Lisdexamfetamine Dimesylate: A New Therapeutic Option for Attention-Deficit Hyperactivity Disorder
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“MPH exerts its action promoting the downregulation of DA and NE transporter (DAT and NET) (protein targets) [139].”
BackgroundInfluential
- Authors
- Strajhar, P., Vizeli, P., Patt, M., Dolder, P. C., Kratschmar, D. V., Liechti, M. E., & Odermatt, A.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Liechti, Matthias E.
- Odermatt, Alex
- ORCID
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 186
- Pages
- 212-225
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2898356502
- Cited by
- 17
- References
- 12
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- edoc (University of Basel)
- Funders
- Swiss Centre of Applied Human Toxicology
- Swiss National Science Foundation (31003A-179400, 320030-170249)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- lisdexamfetamine, d-amphetamine, plasma steroid levels, hypothalamic-pituitary-adrenal axis, ACTH, glucocorticoids, androgens, progesterone, attention deficit hyperactivity disorder, substance abuse risk, pharmacokinetics, healthy volunteers, methylphenidate, MDMA, lysergic acid diethylamide
- MeSH terms
- Lisdexamfetamine Dimesylate, Adrenocorticotropic Hormone, Adult, Central Nervous System Stimulants, Dextroamphetamine, Double-Blind Method, Female, Humans, Male, Steroids, Placebo Effect, Cross-Over Studies, Young Adult
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