3Z Pharmaceuticals, a CNS-focused therapeutic development specialist, today announced the publication of a groundbreaking study in The Journal of Pharmacology and Experimental Therapeutics, unveiling novel insights into the metabolic mechanisms of ADHD treatments. This research, utilizing untargeted metabolomic and lipidomic profiling, addresses a critical knowledge gap in ADHD treatment. It reveals a convergence of molecular pathways among stimulant and non-stimulant ADHD medications and supports 3Z's earlier announced discovery of amlodipine as an L-type calcium channel blocker candidate.

ADHD is a highly prevalent neurodevelopmental disorder with complex underlying mechanisms and limited treatment options. While both stimulant and non-stimulant medications are widely used, their precise metabolic effects on the brain remain poorly understood.

"This study represents a major leap forward in our understanding of ADHD therapeutics," commented Dr. Karl Karlsson, CEO of 3Z Pharmaceuticals, emphasizing the study's significance, "By leveraging advanced metabolomics and lipidomics, we have uncovered a shared metabolic signature across treatments—highlighting the potential of L-type calcium channel modulation as the foundation for a new non-stimulant ADHD therapy. These findings not only validate our drug discovery platform but also pave the way for much-needed new treatment options."

To bridge this gap, 3Z Pharmaceuticals employed an advanced systems biology approach, integrating cross-species analysis using the zebrafish adgrl3.1 ADHD model with targeted metabolomic profiling to explore common metabolic pathways underlying ADHD therapeutics.

Key Findings from the Study:

● Metabolic Pathway Convergence: The study demonstrated that existing ADHD treatments—methylphenidate, guanfacine, and atomoxetine—as well as the novel candidate amlodipine, modulate share metabolic pathways related to amino acid and lipid metabolism. These include glycine, serine, threonine, lysophosphatidylcholine, and sphingomyelin metabolism.

● Systemic impact: Rather than acting through distinct, isolated mechanisms, ADHD medications appear to exert a broader, systemic impact on neurotransmitter precursors, oxidative stress markers, and energy metabolism.

● Amlodipine's Overlapping Effects with ADHD Medications: The metabolic profile of amlodipine significantly overlapped with that of established ADHD treatments, supporting L-type calcium channel engagement as a potential therapeutic pathway for ADHD.

Building on these findings, 3Z Pharmaceuticals is advancing its metabolomics-driven approach to CNS drug discovery, focusing on refining therapeutic targets and optimizing treatment strategies for future clinical development.

About 3Z Pharmaceuticals

3Z Pharmaceuticals, based in Reykjavik, Iceland, identifies and advances next-generation therapies for CNS disorders through both novel discovery and strategic repurposing. The company is pioneering a state-of-the-art drug development platform that integrates high-throughput screening, multi-omics, and AI analytics.

With a strong focus on translational validation, 3Z de-risks CNS drug development by combining multi-species assessment with human Mendelian randomization, polygenic risk scoring, and genetic studies to enhance clinical predictability.