REYKJAVIK, Iceland, Feb. 17, 2025 /PRNewswire/ -- 3Z Pharmaceuticals today announced the publication of a transformative study in Neuropsychopharmacology, highlighting compelling scientific evidence that positions the mechanisms engaged by amlodipine, an L-type calcium channel blocker (LTCC), as a foundation for a novel therapy for ADHD. The findings provide robust validation of 3Z's cutting-edge high-throughput drug discovery platform and introduce new avenues for non-stimulant-based ADHD treatment.
ADHD is a prevalent neurodevelopmental disorder with limited treatment options. Current stimulant medications, such as methylphenidate, offer benefits to some but are often associated with side effects, abuse potential, and a high non-response rate. 3Z Pharmaceuticals is committed to addressing these gaps by pioneering alternative, non-stimulant therapeutics.
In this newly published study, researchers at 3Z, integrated cross-species behavioral assays, Mendelian Randomization analysis, and human genetic data to demonstrate amlodipine's therapeutic potential. Key findings include:
- Behavioral Rescue in ADHD Models: Amlodipine significantly reduced hyperactivity in Spontaneously Hypertensive Rats and improved impulsivity in the adgrl3.1-/- zebrafish model of ADHD, providing cross-species validation of its efficacy.
- Blood-Brain Barrier Penetration & Neural Impact: Surprisingly traditional penetration studies confirmed that amlodipine crosses the blood-brain barrier, where it modulates neuronal activation, countering the assumption of poor brain penetration.
- Genetic Evidence via Mendelian Randomization: Human genetic analysis linked ADHD risk to variations in LTCC genes (CACNA1C, CACNB1, CACNA2D3), which are direct targets of amlodipine, reinforcing its mechanistic potential in ADHD therapy.
- Clinical Relevance in Human Populations: Polygenic risk score analysis using the UK Biobank demonstrated that individuals with a high ADHD genetic burden who were prescribed amlodipine exhibited reduced ADHD-related symptoms, independent of its antihypertensive effects.
Dr. Karl Karlsson a neuroscientist, CEO of 3Z Pharmaceuticals and Professor of Biomedical Engineering at Reykjavik University, commented on the study's impact:
"This research represents a paradigm shift in ADHD therapeutics. Our findings not only validate the mechanism impacted by amlodipine as a promising candidate for non-stimulant ADHD treatment but also underscore the power of our high-throughput screening and genetic modeling approaches, performed in close alliance with biotx.ai. This is an exciting step forward in our mission to deliver more effective and well-tolerated treatments for ADHD."
Building on these findings, 3Z Pharmaceuticals is advancing a variant of the therapeutic towards clinical development, leveraging its established safety profile and precise mechanism of action to introduce transformative ADHD therapy.
Media Contact:
Name: Karl Ægir Karlson
Title: CEO
3Z Pharmaceuticals
Email: Karlsson@3z.is
Phone: +354-8256467
Link to paper: https://www.nature.com/articles/s41386-025-02062-x
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