Reykjavik, Iceland, April 25, 2026

3Z Pharmaceuticals, a CNS-focused therapeutic development specialist, today announced the publication of a new review in The Journal of Pharmacology and Experimental Therapeutics, setting out a mechanistic and translational case for repurposing amlodipine, and specifically its S-enantiomer, S-amlodipine, as a nonstimulant treatment for ADHD. The article, “Reinventing amlodipine,” brings together genetic, preclinical, and population-level evidence into a systems-level framework and lays out a focused roadmap toward clinical testing.

ADHD is a highly prevalent neurodevelopmental disorder, yet current pharmacotherapy remains limited. Stimulants carry tolerability and abuse-risk concerns, available nonstimulants show modest efficacy, and roughly a quarter of patients respond to neither class, leaving a clear need for mechanistically distinct, well-tolerated treatment options.

Amlodipine, a widely prescribed L-type calcium channel (LTCC) blocker long used to treat hypertension, has historically been assumed to act only at the periphery. The review challenges that assumption, drawing on recent pharmacokinetic evidence that amlodipine crosses the blood-brain barrier and engages LTCCs within the central nervous system.

Key points from the review

A systems-level mechanism: The authors propose that central LTCC modulation by amlodipine can stabilize dopaminergic and noradrenergic signaling, restore D2-autoreceptor feedback, support synaptic plasticity, and dampen neuroinflammation, processes central to ADHD.

Convergent preclinical evidence: Amlodipine rescues ADHD-relevant hyperactivity and impulsivity in zebrafish and rat models and shifts ADHD-associated metabolic pathways toward healthy profiles.

A population-level signal: Analyses in genetically at-risk individuals point to reduced ADHD-associated traits among those taking amlodipine, independent of its blood pressure-lowering effects.

A focus on S-amlodipine: With roughly 1,000-fold higher LTCC affinity and fewer off-target liabilities than the R-enantiomer, S-amlodipine emerges as the rational development candidate.

The review concludes by outlining the next steps the company sees as critical: direct S- versus R-amlodipine comparisons, mechanistic dissection of LTCC subtypes in attention circuits, and controlled clinical trials to evaluate efficacy and safety in well-characterized ADHD populations.

Read the full review (open access)

Building on this framework, 3Z Pharmaceuticals continues to advance its mechanism-driven repurposing strategy in CNS drug discovery, with S-amlodipine as a priority program.

Contact

Karl Karlsson

CEO, 3Z Pharmaceuticals

karlsson@3z.is

+354 825 66467