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Dihexa

Emerging research

Synaptogenic Peptide | Cognitive Enhancement

CognitiveLongevity

Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently enhances cognitive function by promoting synaptogenesis.

Molecular & research data

Sequence
Hexanoyl-Tyr-Ile-Ahx-NH2
Molecular weight
504.7 Da
Half-life
8-12 days
Primary targets
bdnf, hgf
Routes (research)
Oral, Injectable, Topical
Storage
Oral: room temperature (2 year shelf life); Injectable lyophilized: 2-8°C; Reconstituted: 2-8°C, use within 30 days

Overview

Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently enhances cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.

Mechanism of action

Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.

Key research findings

  • Dramatic synaptogenesis promotion
  • 10 million times more potent than BDNF
  • Cognitive enhancement and memory improvement
  • Neuroprotection and potential neuroregeneration
  • Applications for Alzheimer’s, TBI, age-related cognitive decline
  • Oral bioavailability

Research applications

Cognitive

  • Memory Enhancement — Improvements in spatial, working, and consolidation demonstrated across animal models.
  • Learning Acceleration — Enhanced acquisition through increased synaptic plasticity.
  • Cognitive Recovery — Restoration in impairment models including scopolamine-induced amnesia.

Neuroprotection

  • Amyloid Reduction — Reduced amyloid burden in Alzheimer’s models.
  • Neuroinflammation Reduction — Decreased neuroinflammation and glial activation.
  • Synaptic Preservation — Protection of synapses in neurodegeneration models.

Neuroplasticity

  • Dendritic Spine Formation — 3-fold increase in dendritic spine formation demonstrated.
  • BDNF Upregulation — Increases brain-derived neurotrophic factor expression.
  • Angiogenesis Promotion — Promotes new blood vessel formation in brain.

Dihexa FAQ

How much more potent is Dihexa than BDNF for synapse formation?+

Dihexa is approximately 10 million times more potent than BDNF at promoting synaptogenesis. This extraordinary potency comes from its picomolar binding affinity for HGF (Kd = 65 pM) and activation of c-Met receptor, enabling profound cognitive effects at very low doses compared to other peptides.

What's the difference between Dihexa and its prodrug Fosgonimeton?+

Fosgonimeton is a prodrug form of Dihexa designed for better pharmacokinetics and clinical development. It showed efficacy in Phase I trials for Alzheimer's disease with normalization of P300 latency. Fosgonimeton may be more stable and bioavailable than raw Dihexa, though research is ongoing.

Does Dihexa cause headaches or other side effects like other nootropics?+

Yes, headaches are the most common side effect reported with Dihexa use, particularly during initial doses. Anxiety, overstimulation, and sleep disruption can also occur due to its potent neuroplastic effects. Starting at low doses (5mg) and timing away from bedtime may minimize these effects.

Is Dihexa safe to combine with other cognitive-enhancing peptides?+

Combining Dihexa with other potent nootropics like Semax or Selank may cause overstimulation or excessive neuroplasticity. Limited human data exists for combinations. If stacking, start conservatively and monitor for increased headaches, anxiety, or mood disturbances indicating neural overstimulation.

References

  1. [1]Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia AgentsJournal of Pharmacology and Experimental Therapeutics
  2. [2]AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling PathwayBrain Research Bulletin
  3. [3]The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met SystemJournal of Pharmacology and Experimental Therapeutics
  4. [4]The Development of Small Molecule Angiotensin IV Analogs to Treat Alzheimer's and Parkinson's DiseasesProgress in Neurobiology
  5. [5]Fosgonimeton Attenuates Amyloid-Beta Toxicity in Preclinical Models of Alzheimer's DiseaseAlzheimer's Research & Therapy
  6. [6]Safety, Tolerability, and Pharmacodynamics of Fosgonimeton in Healthy Volunteers and Alzheimer's Subjects: Phase I Clinical TrialJournal of Alzheimer's Disease
  7. [7]Fosgonimeton Promotes Neurotrophic and Procognitive Effects in Models of DementiaNeurotherapeutics

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Last reviewed: 2026-06-26. Information is provided for research and educational reference only — see our disclaimer.