Dihexa
Also known as: PNB-0408, Angiotensin IV analog, Synaptogenic peptide
Overview
Dihexa (PNB-0408) is a small hexapeptide derived from angiotensin IV that exhibits extraordinarily potent synaptogenic activity—reportedly 10 million times more potent than BDNF by molar concentration in promoting synapse formation in hippocampal neuronal cultures. Developed at Washington State University, Dihexa works through a novel mechanism involving hepatocyte growth factor (HGF) and its receptor c-Met rather than through classical peptide hormone receptors. It crosses the blood-brain barrier and is orally active, making it a compelling candidate for neurodegenerative disease treatment.
Mechanism of Action
Dihexa acts by binding to and potentiating the hepatocyte growth factor (HGF) signaling system. It activates or sensitizes HGF/c-Met receptor pathway signaling in hippocampal neurons, which drives synaptic protein expression (PSD-95, synapsin), dendritic spine formation, and synaptogenesis. This occurs independently of classical angiotensin receptor signaling despite the structural relationship to angiotensin IV. The c-Met pathway activation leads to downstream ERK/MAPK and PI3K/Akt signaling, stimulating neuronal gene expression programs associated with synaptic plasticity and cognitive function.
Potential Benefits
- Extraordinary potency in synaptogenesis (10 million× BDNF by molar mass in vitro)
- Cognitive enhancement in rodent models of dementia
- Oral bioavailability with CNS penetration
- Synaptic density restoration in models of age-related cognitive decline
- Novel c-Met mechanism distinct from other nootropics
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Beginner | 200-250 mcg daily — assess tolerance for 1-2 weeks |
| Intermediate | 300-500 mcg daily |
| Advanced | 500-1000 mcg daily, split AM/PM |
| Cycle Duration | 4-8 weeks |
Research-community dosing based on published protocols. Consult a qualified clinician before use.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Subcutaneous Injection High — systemic distribution
Most common administration route for research peptides. Inject into abdominal fat, thigh, or upper arm. Rotate sites. standard research dose.
Intramuscular Injection High — with slightly faster onset than SC
Alternative route when deeper delivery or faster absorption is desired. Less commonly used than SC for most research peptides.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving Dihexa:
Nootropic Stack
Combines Dihexa with Semax (BDNF/cognition) and Selank (anxiolytic) for balanced cognitive enhancement and stress resilience.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Refrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution. |
|---|
Typical vial sizes: 5 mg. Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.
Need exact syringe measurements?
Amino Acid Sequence
Modified angiotensin IV hexapeptide with structural modifications for stability
Side Effects & Safety
- Unknown long-term safety profile
- Theoretical concern: potential oncogenic signaling via c-Met activation
- Human safety data lacking
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Pregnancy / Lactation
Bleeding Disorders
Active Skin Infection at Injection Site
Pharmacokinetics
| Half-Life | ~10-12 hours (oral, estimated) |
|---|---|
| Storage | Store at room temperature (15-25°C) in a dry, dark place. Keep tightly closed. Do not refrigerate capsules. |
Synergistic Compounds
The following compounds have been studied alongside Dihexa for potential complementary or synergistic effects:
Learn More
References & Further Reading
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