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Nootropic & CNSResearch strength: PreliminaryEvidence: Preliminary

Dihexa

Dihexa (angiotensin IV analogue)

Also known as: PNB-0408

An experimental angiotensin-derived peptide reported to be an extremely potent promoter of new synapse formation in animal models of cognition.

Overview

Dihexa is a small peptide derived from angiotensin IV, developed to cross into the brain and promote the formation of new synaptic connections. In rodent models of Alzheimer-like impairment it improved cognition at very low doses by potentiating hepatocyte growth factor signaling. It is experimental, with no human clinical trials, so the evidence is preliminary.

Mechanism of action

Potentiates hepatocyte growth factor and its c-Met receptor to drive synaptogenesis, the formation of new synaptic connections.

Key studies & citations

  • Animal2013

    Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents

    Introduced dihexa, an orally active, blood-brain-barrier-permeant AngIV analogue that reversed scopolamine-induced memory deficits and increased hippocampal synaptogenesis in rats. The journal issued an Expression of Concern for this paper in 2021.

    Journal of Pharmacology and Experimental Therapeutics
  • Review2015

    The brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer's disease

    Review by the developers describing dihexa as an HGF/c-Met potentiator that induces dendritic arborization and synaptogenesis in animal models; no human trials.

    Journal of Alzheimer's Disease

Frequently asked questions

Has dihexa been tested in people?

No. The evidence is from animal studies only. There are no human clinical trials, so it is experimental.

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