Dihexa

Dihexa (N-hexanoic-Tyr-Ile-(6) amino hexanoic amide) is a first-in-class angiotensin-based small molecule derived from the pre-prototype molecule Nle1-angiotensin IV, that is orally active and penetrates the blood-brain barrier. ^[1] Dihexa is a neuroactive peptide that enhances brain-derived neurotrophic factor and the hepatocyte growth factor (HGF)/c-Met pathways critical to neuroplasticity. ^[2]

Dihexa stimulates the hepatocyte growth factor (HGF)/c-Met receptor system, whose activation stimulates mitogenesis, motogenesis, morphogenesis, stem cell differentiation and neurogenesis, and protects against tissue insults in a wide range of cells including neurons. ^[1] In animal studies Dihexa has been shown to induce dendritic arborization and synaptogenesis, facilitating the formation of new functional synaptic connections and augmenting memory consolidation and retrieval. ^{[1] [3]}

The evidence for Dihexa is preclinical and experimental: it has shown promise in animal models of Alzheimer's disease by augmenting synaptic connectivity, but no clinical trials have been reported. ^{[1] [2]} In a systematic review of experimental non-human studies, eight of nine studies in models of cognitive deficit found that angiotensin IV and its analogs, including dihexa, improved performance on spatial working memory and passive avoidance tasks. ^[4]