Noopept / Semax / Selank
Class Russian regulatory peptide nootropics
Status Approved Rx in Russia/CIS; research/grey in USA; Semax: WADA S2 prohibited
TL;DR
Three Russian-developed synthetic regulatory peptides with epigenetic/transcriptomic effects far beyond classical nootropics. All are adaptive modulators — upregulate NMDA/BDNF only in deficit states, downregulate when baseline is normal. Noopept: oral prodrug (cycloprolylglycine active metabolite). Semax: ACTH analog, primarily ischemic stroke. Selank: tuftsin analog, anxiolytic without dependence. Key stack logic with NAD+: Selank/Noopept ↓ IL-6 → ↓ CD38 → less NAD degradation → NMN more efficient.
Three Compounds
| Noopept | Semax | Selank | |
|---|---|---|---|
| Structure | N-phenylacetyl-L-prolylglycine ethyl ester | ACTH(4-10) analog + PGP | Tuftsin analog + PGP |
| Route | Oral / sublingual | Intranasal / SubQ | Intranasal / SubQ |
| Primary target | Sigma-1R / cPG metabolite | MC4R (melanocortin) | Enkephalinase inhibition |
| Key effect | BDNF/NGF, neuroprotection | Stroke recovery, BDNF | Anxiolysis, IL-6 suppression |
| WADA status | Monitored (S6) | Prohibited (S2) | Monitored |
Key Mechanisms
Adaptive NMDA Modulation
All three: cortical NMDA ↓ (anti-excitotoxic, universal); hippocampal NMDA ↑ only in deficit subjects. Pattern: correct deficiency without forcing universal changes.
Neurotrophin Induction
- Noopept chronic (28-day): sustained BDNF in cortex + hippocampus — no tolerance development
- Upregulates NGF, NT-3, NT-4 → nerve outgrowth and maintenance
Semax (ACTH analog — MC4R)
- Primary Russian clinical use: ischemic stroke treatment/rehab
- Reverses 394 DEGs in tMCAO model; suppresses MMP-9, c-Fos, JNK
- fMRI: measurable whole-brain connectivity changes within 5–20 minutes intranasal
- CRH mRNA reduction → HPA axis damping
Selank (Tuftsin analog)
- Enkephalinase inhibition (IC50 15 μM) → amplifies endogenous opioid stress regulation
- Completely inhibits IL-6 gene expression at elevated baseline
- GABAergic anxiolysis without sedation, amnesia, dependence, or withdrawal
- Modulates Th1/Th2 balance; alters gut/oral microbiota under stress
Dosing
| Compound | Route | Dose | Frequency |
|---|---|---|---|
| Noopept | Oral / sublingual | 10–30 mg/day (divided) | BID–TID |
| Semax | Intranasal | 0.5–3 mg/day | 1–3×/day |
| Semax | SubQ | 0.5–1 mg/day | Once daily |
| Selank | Intranasal | 0.25–3 mg/day | 1–3×/day |
| Selank | SubQ | 0.25–1 mg/day | Once daily |
Cycle: 2–4 weeks on / 2 weeks off (all three)
Key Stacks
| Stack | Rationale |
|---|---|
| + NAD+ precursors (NMN/NR) | Selank/Noopept ↓ IL-6 → ↓ CD38 expression → less NAD+ degradation → NMN more efficient SIRT1 activation |
| + BPC-157 | Holistic neuro-somatic repair; BPC counteracts dopamine neuroleptic damage; TBI recovery protocol |
| + Racetams | Structural/transcriptomic support (peptides) prevents racetam-driven excitotoxic burnout |
Links
- Peptides MOC
- Tissue Repair — BPC-157 overlaps here (neuroprotection + tissue repair)
Source: Gemini Deep Research · Zakusov Research Institute · PeptideDosages.com 2026-03-20