Dihexa Reconstitution Calculator

No. Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide; PNB-0408) is not FDA-approved, has no human clinical trial data, and remains a research compound [3, 10]. All existing evidence is preclinical: rodent models, zebrafish, and cell culture (animal) [5, 8, 9].

Dihexa was engineered specifically to overcome the gut and blood-brain barriers that limited its parent peptide Nle1-angiotensin IV (animal) [1, 3]. Oral dosing produced procognitive and synaptogenic effects in scopolamine-treated and aged rats, and restored memory in APP/PS1 mice [1, 5]. Injections (s.c./i.p./local) at 2–4 mg/kg were used in rat nerve-repair studies. Oral has the strongest preclinical support; no human pharmacokinetic data exist for either route.

Dihexa binds hepatocyte growth factor (HGF) with high affinity, inducing c-Met receptor phosphorylation even at subthreshold HGF levels and augmenting HGF-driven cell responses (in-vitro) [2, 8]. It triggers hippocampal dendritic spine and synapse formation (spinogenesis/synaptogenesis) similar to HGF itself; its memory-enhancing effect is abolished by an HGF antagonist or c-Met knockdown. In APP/PS1 Alzheimer-model mice it activates the PI3K/AKT pathway, lowers pro-inflammatory IL-1β and TNF-α, raises anti-inflammatory IL-10, and reduces glial activation (animal).

No human dose data exist. Rat nerve-repair studies used 2–4 mg/kg; zebrafish hair-cell protection peaked at 1 µM. Community protocols typically use 10–40 mg/day oral, cycled (community protocol). Direct per-kg extrapolation from rats (e.g., 160–320 mg at 80 kg) substantially exceeds community practice; human oral bioavailability is unmeasured. Storage: keep dry powder cool, dry, and dark; refrigerate reconstituted solutions and use promptly (practical guidance, community protocol).

In animal models, often yes. Dihexa reverses scopolamine-induced memory deficits, improves maze performance in aged rats, and augments synaptogenesis (animal). A systematic review found angiotensin IV analogs including Dihexa improved spatial working memory or passive avoidance in 8 of 9 cognitive-deficit studies. In APP/PS1 mice it restored spatial learning and raised neuronal and synaptic protein (synaptophysin) markers. It failed, however, against 3-nitropropionic acid-induced Huntington's-like deficits in rats. No human efficacy trials exist.

Dihexa is distinct: orally active, metabolically stabilized, and blood-brain-barrier penetrant, unlike native angiotensin IV (animal) [1, 3]. Neuroactive peptides such as semax and selank are described as acting through brain-derived neurotrophic factor (BDNF) and HGF/c-Met-associated neuroplasticity pathways, while Dihexa engages HGF/c-Met directly by binding HGF (in-vitro). No head-to-head comparisons against any other peptide exist.

No human safety data. Rat studies up to 16 weeks at 2–4 mg/kg reported no obvious toxicity but were not designed to document long-term safety (animal). Pregnancy and breastfeeding: entirely unstudied, do not use. Mechanistic caution: HGF/c-Met signaling drives cell growth, motility, and tissue remodeling in many organs; consequences of chronic receptor activation are unknown.

No human duration data. Community practice is 4–8-week cycles with off-periods (community protocol). Cycling reflects the unknown safety of sustained HGF/c-Met activation rather than any demonstrated tolerance effect.