Peptide Schedule
DihexaSmall moleculeNo amino acid sequence. Icon reflects category theme only.Dihexa
Benefits
About Dihexa
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, also called PNB-0408) is a small peptidomimetic derived from angiotensin IV. It was developed at Washington State University as a metabolically stable analog designed to cross the blood-brain barrier and activate the hepatocyte growth factor (HGF)/c-Met signaling pathway. In animal models, Dihexa has been shown to promote synaptogenesis — the formation of new functional connections between neurons — at picomolar concentrations. Rat studies demonstrated reversal of scopolamine-induced cognitive deficits and improved spatial memory in aged animals. All existing evidence comes from preclinical animal research. No human clinical trials have been conducted, and the long-term safety profile is unknown. Because Dihexa activates the HGF/c-Met proto-oncogenic pathway, there is a theoretical concern about tumor promotion with sustained use. This compound should be considered strictly experimental.
Who Should Consider Dihexa
- Researchers investigating HGF/c-Met pathway activation
- Individuals exploring experimental nootropics under medical supervision
- Adults interested in preclinical neuroprotective compounds
- Those studying age-related cognitive decline interventions
How Dihexa Works
Dihexa binds directly to hepatocyte growth factor (HGF) with high affinity (Kd ~65 pM) and allosterically potentiates its activity at the c-Met receptor. When subthreshold concentrations of HGF are present, Dihexa amplifies c-Met phosphorylation, triggering downstream PI3K/AKT signaling. This cascade stimulates dendritic spine formation and new synapse development (synaptogenesis) in hippocampal neurons. The compound also reduces neuroinflammation by suppressing pro-inflammatory cytokines (IL-1B, TNF-a) and elevating anti-inflammatory IL-10. Unlike its parent molecule angiotensin IV, Dihexa resists enzymatic degradation, giving it a prolonged circulating half-life and oral bioavailability.
What to Expect
Anecdotal reports suggest initial improvements in focus and mental clarity. No clinical data supports this timeline. Effects may be placebo.
Animal studies show measurable synaptogenesis and improved spatial memory within this window. Anecdotal reports describe enhanced learning capacity and memory recall.
In rat models, peak cognitive enhancement and synaptic remodeling observed by this period. Recommended cycle endpoint.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 5mg | Daily |
| Moderate | 10mg | Daily |
| Aggressive | 20mg | Daily |
Note: Angiotensin IV analog. HGF/c-Met activator. Also known as PNB-0408. Preclinical only — no human trials exist. Oral or subcutaneous. Doses in mg range, not mcg like most peptides. Cycle 6 weeks on, 6 weeks off.
How to Inject Dihexa
Oral: take on an empty stomach once daily. Subcutaneous: inject into abdominal fat once daily, rotating injection sites. Doses are in milligrams (not micrograms) — do not confuse with typical peptide dosing. Start at the lowest effective dose. This is a research compound with no established human dosing guidelines.
Cycling Protocol
Cycling recommended to prevent receptor desensitization. Due to lack of human safety data, longer cycles are not advised. Monitor for mood changes and discontinue if side effects emerge.
Pharmacokinetics
Source: McCoy et al. 2013 (PMID 23055539): t1/2 = 12.68 days IV in rats. No human PK data.
Loading the interactive decay curve.
Side Effects
Limited safety data — all from animal studies and anecdotal reports. Reported anecdotally: nervousness, irritability, insomnia, and mood changes. Theoretical oncogenic risk from sustained HGF/c-Met activation. No human toxicology studies have been performed.
Contraindications
- Any active or history of cancer — HGF/c-Met pathway activation may promote tumor growth
- Pregnancy or breastfeeding — no reproductive toxicology data exists
- Individuals under 25 — brain development still ongoing
- Known hypersensitivity to angiotensin-derived compounds
- Liver disease — HGF is a hepatocyte-targeted growth factor
Drug Interactions
- ACE inhibitors and ARBs — potential interaction via the renin-angiotensin system
- Anticoagulants — HGF/c-Met signaling may affect platelet function; monitor closely
- Cancer therapeutics (c-Met inhibitors such as crizotinib, cabozantinib) — direct pharmacological antagonism
- Other nootropics or cognitive enhancers — no interaction data available; use caution with stacking
Storage & Stability
Related Peptides
References
- Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents (McCoy et al., J Pharmacol Exp Ther, 2013)PubMed 23055539
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway (Sun et al., Brain Sciences, 2021)PubMed 34827486
- The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease (Wright & Harding, CNS Drugs, 2015)PubMed 25649658