Dihexa

In simple words

Dihexa is a small, stable molecule resembling a fragment of the hormone angiotensin that enters the brain and works when taken by mouth. It is studied in animals as a substance that stimulates the formation of new connections between nerve cells, including in models of Alzheimer's disease.

What this molecule is

N-hexanoyl-Tyr-Ile-6-aminohexanoic amide. A metabolically stable analog of AngIV (angiotensin IV). ~507 Da. Crosses the BBB. Orally active. Not covered in foreign peptide guides.

Why it is studied

A pro-cognitive peptide acting through HGF/c-Met activation. 10 million times more potent than BDNF in synaptogenesis in vitro (EC₅₀). ×3 growth of dendritic spines in APP/PS1 mice (Alzheimer's model). Synergistically stronger than all other nootropics in the strength of its pro-cognitive effect in animal models. OUR EXCLUSIVE.

How it works

AngIV analog → c-Met receptor (HGF receptor) → PI3K/Akt + RAS/ERK → ↑synaptogenesis, ↑dendritic spinogenesis, ↑LTP. Blocking c-Met = complete absence of effect. The mechanism is fundamentally different from BDNF/TrkB.

Doses used in studies

Researchers' practice describes 10-20 mg orally or 0.5-1 mg SC. Not clinically validated. Orally active (a rarity).

Combined with in studies

• P-21/P021 — HGF + BDNF — a double neurotrophic hit
• Semax — BDNF, a different receptor
• Cerebrolysin — neurotrophins + HGF

Level of evidence

Level C Animal studies. Effects have been shown in animals. Whether they carry over to humans has not been proven. animals only. No clinical data. But the mechanism is unique.

Important to know

🔴 c-Met is a proto-oncogene. Caution in oncology. “10 million times more potent than BDNF” = EC₅₀ in vitro, not a clinical effect. No clinical data. Research only.

Studies in PubMed

1. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. (J Pharmacol Exp Ther, 2013)
2. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. (J Pharmacol Exp Ther, 2014)
3. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. (Brain Sci, 2021)
4. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. (Neurosci Biobehav Rev, 2018)
5. The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease. (J Alzheimers Dis, 2015)
6. The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases. (Prog Neurobiol, 2015)