ArticleNeuropsychiatric disease and treatment2014
Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells.
Article in Neuropsychiatric disease and treatment, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Acute effects of lisdexamfetamine and D-amphetamine on social cognition and cognitive performance in a placebo-controlled study in healthy subjects.Psychopharmacology · 2018Trial
- Trial
- Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence.BMC psychiatry · 2016Trial
- Effects of exposure to lisdexamfetamine dimesylate on hepatic parameters of pubertal rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Bioactivation and Metabolism of Amino Acid MDMA Prodrugs in Zebrafish Embryos, Human Liver S9, Whole Blood, and Microdosed Human Urine.Drug testing and analysis · 2026Article
- Article
- Multidimensional Evaluation of Lisdexamfetamine: Pharmacology, Therapeutic Use, Toxicity and Forensic Implications.Basic & clinical pharmacology & toxicology · 2025Review
- Understanding the delivery technology used in ADHD stimulant medications can help to individualize treatment.CNS spectrums · 2025Review
- Acute anxiogenic effect of lisdexamphetamine dimesylate in zebrafish: implications of off-label cognitive enhancement use.Toxicology research · 2025Article
- Effect of bariatric surgery on the pharmacokinetics of drugs used for attention-deficit hyperactivity disorder-A case series.Basic & clinical pharmacology & toxicology · 2025Article
- Prospects for new drugs to treat binge-eating disorder: Insights from psychopathology and neuropharmacology.Journal of psychopharmacology (Oxford, England) · 2022Review
- New Drugs to Treat ADHD: Opportunities and Challenges in Research and Development.Current topics in behavioral neurosciences · 2022Review
- Single Dose Comparative Bioavailability Study of Lisdexamfetamine Dimesylate as Oral Solution Versus Reference Hard Capsules in Healthy Volunteers.Frontiers in pharmacology · 2022Article
- Development of the Korean Practice Parameter for Adult Attention-Deficit/Hyperactivity Disorder.Soa--ch'ongsonyon chongsin uihak = Journal of child & adolescent psychiatry · 2020Article
- Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects.Frontiers in pharmacology · 2017Article
- Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration of Efficacy.Clinical drug investigation · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lisdexamfetamine dimesylate (LDX) is approved as a once-daily treatment for attention-deficit/hyperactivity disorder in children, adolescents, and adults in some countries. LDX is a prodrug comprising d-amphetamine covalently linked to l-lysine via a peptide bond. Following oral administration, LDX is rapidly taken up from the small intestine by active carrier-mediated transport, probably via peptide transporter 1. Enzymatic hydrolysis of the peptide bond to release d-amphetamine has previously been shown to occur in human red blood cells but not in several other tissues. Here, we report that LDX hydrolytic activity resides in human red blood cell lysate and cytosolic extract but not in the membrane fraction. Among several inhibitors tested, a protease inhibitor cocktail, bestatin, and ethylenediaminetetra-acetic acid each potently inhibited d-amphetamine production from LDX in cytosolic extract. These results suggest that an aminopeptidase is responsible for hydrolytic cleavage of the LDX peptide bond, although purified recombinant aminopeptidase B was not able to release d-amphetamine from LDX in vitro. The demonstration that aminopeptidase-like activity in red blood cell cytosol is responsible for the hydrolysis of LDX extends our understanding of the smooth and consistent systemic delivery of d-amphetamine by LDX and the long daily duration of efficacy of the drug in relieving the symptoms of attention-deficit/hyperactivity disorder.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.