DihexaAlso known as: PNB-0408, N-hexanoic-Tyr-Ile-γ-Ahx-(6) amino hexanoic amide

Mechanism of Action

Dihexa is an angiotensin IV derivative peptide that exhibits strong affinity for hepatocyte growth factor (HGF) and activates the HGF/c-Met signaling pathway. This activation promotes synaptogenesis, neurogenesis, and neuronal survival by mimicking or potentiating brain-derived neurotrophic factor (BDNF)-like activity, enhancing synaptic connectivity and cognitive plasticity. It crosses the blood-brain barrier efficiently and influences vascular physiology to improve cerebral blood flow, aiding neuronal communication and cognitive functions.

Reported Research Benefits

Investigated primarily as a nootropic agent for cognitive enhancement, supporting memory, learning, mental clarity, synaptic connectivity, and neuronal health. It is also studied for neuroprotective effects, promoting recovery from neurodegenerative conditions and possibly enhancing mental vitality and stress resilience.

Dosing Protocol & Reconstitution

In research and nootropic use, Dihexa is typically dosed around 5-10 mg per day orally, often administered in capsules. Clinical dosing regimens remain under investigation, but 10 mg daily dosages are referenced in experimental and consumer contexts.

Research Notes

Preclinical studies show Dihexa’s neurotrophic activity exceeds that of traditional neurotrophins like BDNF in vitro. It displays robust synaptogenic effects and potential for neural repair in models of cognitive deficit. The peptide is stable with a moderate half-life allowing once-daily dosing. More clinical research is needed to fully characterize its efficacy and safety profile.

Research Summary

Dihexa is a small peptide angiotensin IV derivative shown in preclinical studies primarily using rodent models to significantly enhance synaptogenesis, cognitive function, and neuroprotection by activating the HGF/c-Met pathway. Unlike traditional neurotrophic factors, Dihexa crosses the blood-brain barrier efficiently, resulting in improved learning, memory, and recovery in models of neurodegeneration and traumatic brain injury. While promising, evidence is limited to preclinical data with no registered clinical trials to date, and thus human efficacy and safety remain to be established. The peptide's potential to mimic BDNF-like activity underscores its therapeutic interest in neurodegenerative diseases and cognitive disorders.

Side Effects & Safety

Current knowledge of Dihexa's safety profile is primarily based on animal studies, with no formal human safety data available. Reported side effects in animal models are minimal; however, theoretical risks include off-target activation of the HGF/c-Met pathway, which is implicated in oncogenesis, warranting caution regarding long-term use. Potential drug interactions have not been extensively studied. There are no known reports of adverse vascular effects despite its influence on cerebral blood flow. Dihexa is not currently regulated or banned by major doping agencies like WADA, but its novel mechanism and unapproved status underscore the need for careful clinical evaluation before widespread use.

Stability & Storage

Refer to research notes

Molecular Data

Sequence: N-hexanoyl-Tyr-Ile-γ-Ahx-amide
Molecular Formula: C43H66N12O9
Molecular Weight: 874.06 g/mol
CAS Number: 1418248-39-8
IUPAC Name: N-hexanoyl-L-tyrosyl-L-isoleucyl-(6-aminohexanoyl)-amide

Primary literature: https://pubmed.ncbi.nlm.nih.gov/?term=Dihexa