Dihexa vs N-Acetyl Selank
A neutral, side-by-side comparison of two nootropic & cognitive peptides — their mechanisms, dosing ranges, administration routes, side effects, and research evidence. For research and educational purposes only.
Dihexa
Dihexa is a synthetic hexapeptide derived from angiotensin IV, developed at Washington State University. It is considered one of the most potent nootropic peptides known — in rodent models it outperforms BDNF itself for synaptogenesis and cognitive enhancement, acting through the hepatocyte growth factor (HGF) / c-Met receptor system. Unlike most nootropics, Dihexa is highly lipophilic and can be administered transdermally or orally.
Full profileN-Acetyl Selank
Acetylated variant of Selank with enhanced stability and bioavailability. The N-acetyl modification protects the peptide from rapid enzymatic degradation, extending its active half-life relative to standard Selank. Provides anxiolytic, nootropic, and immunomodulatory effects comparable to or exceeding standard Selank with potentially greater duration from each dose.
Full profile| Dihexa | N-Acetyl Selank | |
|---|---|---|
| Category | Nootropic & Cognitive | Nootropic & Cognitive |
| Also known as | PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide | Selank-A, N-Ac-Selank, acetylated selank, N-acetyl selank |
| Evidence | Preclinical only | Research-stage |
| Dosing range | 10mg–20mg mg, Once daily (or every other day — long-lasting effects) | 100mcg–500mcg mcg, 1–2x daily intranasal |
| Administration | Oral (capsule), Transdermal (cream/lotion — lipophilicity makes this effective), Subcutaneous injection (less common) | Intranasal spray, Subcutaneous injection |
| Key side effects | Potential for pro-proliferative effects — HGF/c-Met pathway promotes cell growth (theoretical cancer concern at high doses), Headache (uncommon), Mental fatigue if overdosed, Long half-life means effects accumulate — take every other day initially | Mild sedation (acute), Fatigue, Headache (rare), Nasal irritation (intranasal route) |
| Cited sources | 2 references | 2 references |
Key differences
- Evidence level differs: Dihexa is preclinical only, while N-Acetyl Selank is research-stage.
- Administration: Dihexa — Oral (capsule), Transdermal (cream/lotion — lipophilicity makes this effective), Subcutaneous injection (less common); N-Acetyl Selank — Intranasal spray, Subcutaneous injection.
- Dosing units differ: Dihexa is dosed in mg, N-Acetyl Selank in mcg — they operate at different scales.
- Frequency: Dihexa is typically Once daily (or every other day — long-lasting effects); N-Acetyl Selank is 1–2x daily intranasal.
How each works
Dihexa
Dihexa (PNB-0408) was developed by Joseph Harding and colleagues at WSU as a metabolically stable angiotensin IV analog. It binds hepatocyte growth factor (HGF), potentiating its interaction with the c-Met receptor — a pathway critical for dendritic branching, synapse formation, and synaptic plasticity. In rodent Alzheimer's and scopolamine-impaired models, Dihexa restored cognitive performance at doses ~7 orders of magnitude lower than BDNF. It readily crosses the blood-brain barrier due to its lipophilicity, unlike BDNF itself.
N-Acetyl Selank
N-Acetyl Selank shares Selank's core mechanism — BDNF/NGF upregulation, enkephalinase inhibition, and GABA-A receptor complex modulation — with improved metabolic stability from the N-terminal acetyl group. The acetyl modification protects against aminopeptidase N and angiotensin-converting enzyme cleavage, extending the peptide's active residence time in neural tissue after intranasal administration.
This comparison aggregates public research and structured profile data for informational purposes only. It is not medical advice and does not recommend either compound for human use. Consult a qualified healthcare provider before considering any peptide.