| Title: | 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 |
| Journal: | Neuropsychopharmacology |
| Published: | 14 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39953207/ |
| DOI: | https://doi.org/10.1038/s41386-025-02062-x |
| URL: | https://doi.org/10.1101/2024.05.30.24308216 |
Publication 14399
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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.</p>
12 Authors
- Haraldur Þorsteinsson
- Hannes A. Baukmann
- Hildur S. Sveinsdóttir
- Dagmar Þ. Halldórsdóttir
- Bartosz Grzymala
- Courtney Hillman
- Jude Rolfe-Tarrant
- Matthew O. Parker
- Justin L. Cope
- Charles N. J. Ravarani
- Marco F. Schmidt
- Karl Æ. Karlsson
1 Application
| Application ID | Title |
|---|---|
| 36226 | Validation and improvement of our Machine Learning approach to analyze interactions in your genotyping/imputation data for better Familial Hypercholesterolemia diagnostics |
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