An angiotensin IV analog reported to be 10 million times more potent than BDNF at promoting synaptogenesis.
Dihexa (PNB-0408) is a small molecule angiotensin IV analog developed at Washington State University by Joseph Harding and colleagues. It has been reported to be approximately 10 million times more potent than BDNF (brain-derived neurotrophic factor) at promoting synaptogenesis — the formation of new synaptic connections in the hippocampus — making it one of the most potent cognitive enhancers ever studied in preclinical models. Dihexa was originally developed as a potential treatment for Alzheimer’s disease and other neurodegenerative conditions, where synapse loss is a primary driver of cognitive decline. Unlike many nootropics that simply modulate neurotransmitter levels, Dihexa appears to promote structural changes in the brain by stimulating the growth of new synaptic connections. Due to its extreme potency, it is used in very small doses and typically in short cycles, as the effects on synaptogenesis may persist for weeks after discontinuation.
* Benefits based on preclinical/animal research unless otherwise noted.
Dihexa binds to hepatocyte growth factor (HGF) and potentiates its interaction with the c-Met receptor tyrosine kinase, a signaling pathway that plays a critical role in neuronal survival, synaptogenesis, and synaptic plasticity in the hippocampus and cortex. Activation of HGF/c-Met signaling triggers downstream cascades including PI3K/Akt and MAPK/ERK pathways, which promote dendritic spine growth, synapse formation, and long-term potentiation (LTP) — the cellular mechanism underlying memory consolidation. Dihexa also demonstrates anti-inflammatory effects in the CNS by reducing microglial activation and neuroinflammatory cytokine production. The compound is orally bioavailable and crosses the blood-brain barrier efficiently, allowing for convenient oral dosing. Its extraordinary potency relative to endogenous BDNF suggests it may act as a positive allosteric modulator of the HGF/c-Met system rather than a simple agonist.
Protocol Notes: Use in short cycles due to potency. Start with lowest dose. Effects may persist for weeks after stopping due to synaptogenesis. Avoid continuous use.
Store at room temperature, away from light and moisture.
When sourcing Dihexa (Capsule) for research purposes, the following quality benchmarks should be verified before use.
Store at room temperature, away from light and moisture.
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Preliminary Evidence — Early-stage research only. Significant uncertainty about efficacy and safety in humans.
Animal & In-Vitro Only — Mechanism observed in cell culture or animal models. No human efficacy data. Not evidence of an effect in humans.
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