PUBLICATION
Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records
- Authors
- Þorsteinsson, H., Baukmann, H.A., Sveinsdóttir, H.S., Halldórsdóttir, D.Þ., Grzymala, B., Hillman, C., Rolfe-Tarrant, J., Parker, M.O., Cope, J.L., Ravarani, C.N.J., Schmidt, M.F., Karlsson, K.Æ.
- ID
- ZDB-PUB-250216-6
- Date
- 2025
- Source
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology : (Journal)
- Registered Authors
- Karlsson, Karl, Parker, Matt, Þorsteinsson, Haraldur
- Keywords
- none
- MeSH Terms
-
- Attention Deficit Disorder with Hyperactivity*/drug therapy
- Attention Deficit Disorder with Hyperactivity*/genetics
- Female
- Rats, Inbred SHR
- Calcium Channel Blockers*/pharmacology
- Calcium Channel Blockers*/therapeutic use
- Mendelian Randomization Analysis
- Male
- Calcium Channels, L-Type*/genetics
- Rats
- Humans
- Animals
- Species Specificity
- Amlodipine*/pharmacology
- Amlodipine*/therapeutic use
- PubMed
- 39953207 Full text @ Neuropsychopharmacology
Citation
Þorsteinsson, H., Baukmann, H.A., Sveinsdóttir, H.S., Halldórsdóttir, D.Þ., Grzymala, B., Hillman, C., Rolfe-Tarrant, J., Parker, M.O., Cope, J.L., Ravarani, C.N.J., Schmidt, M.F., Karlsson, K.Æ. (2025) Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. :.
Abstract
ADHD is a chronic neurodevelopmental disorder that significantly affects life outcomes, and current treatments often have adverse side effects, high abuse potential, and a 25% non-response rate, highlighting the need for new therapeutics. This study investigates amlodipine, an L-type calcium channel blocker, as a potential foundation for developing a novel ADHD treatment by integrating findings from animal models and human genetic data. Amlodipine reduced hyperactivity in SHR rats and decreased both hyperactivity and impulsivity in adgrl3.1-/- zebrafish. It also crosses the blood-brain barrier, reducing telencephalic activation. Crucially, Mendelian Randomization analysis linked ADHD to genetic variations in L-type calcium channel subunits (α1-C; CACNA1C, β1; CACNB1, α2δ3; CACNA2D3) targeted by amlodipine, while polygenic risk score analysis showed symptom mitigation in individuals with high ADHD genetic liability. With its well-tolerated profile and efficacy across species, supported by genetic evidence, amlodipine shows potential to be refined and developed into a novel treatment for ADHD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping