3Z Pharmaceuticals 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.