Semax & Selank: The Frontier of Nootropic Peptides
Comparing the mechanisms of ACTH-derived analogues in cognitive enhancement and anxiolytic models.
Background
Semax and Selank are synthetic peptides developed in the 1980s and 1990s at the Russian Academy of Sciences Institute of Molecular Genetics. Both are built on ACTH-derived sequences but engineered for very different pharmacology — Semax for cognitive/neuroprotective research, Selank for anxiolytic/immunomodulatory research. Both are approved pharmaceuticals in Russia for specific indications and are used as research tools elsewhere (including extensive publication in neuroscience and pharmacology journals).
This article compares their mechanisms and typical research applications.
Semax: the cognitive peptide
Semax is a synthetic heptapeptide based on ACTH(4-7) with a C-terminal proline-glycine-proline (PGP) extension that confers enzymatic stability.
- Sequence: Met-Glu-His-Phe-Pro-Gly-Pro (7 aa)
- Molecular weight: ~814 Da
- CAS: 80714-61-0
- Pharmacological relatives: ACTH-derived peptides (without adrenal effects due to modification)
Mechanism:
- BDNF upregulation — brain-derived neurotrophic factor expression in cortex and hippocampus
- NGF elevation — nerve growth factor in neural tissue
- Dopaminergic modulation — alters striatal and prefrontal dopamine turnover
- Serotonergic effects — 5-HT receptor modulation
- Neuroprotection — reduces oxidative stress markers in ischemic/hypoxic models
- Anti-inflammatory — reduces TNF-α, IL-1β in neural inflammation models
- Enkephalin-related pathways — interacts with opioid receptor systems indirectly
Typical research applications: ischemic stroke models, traumatic brain injury recovery, ADHD-related research, memory/learning paradigms (Morris water maze, object recognition), optic nerve damage, age-related cognitive decline.
Selank: the anxiolytic peptide
Selank is a synthetic heptapeptide derived from tuftsin (Thr-Lys-Pro-Arg, a natural immunomodulatory tetrapeptide) with a PGP extension.
- Sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro (7 aa)
- Molecular weight: ~751 Da
- CAS: 129954-34-3
- Pharmacological relatives: tuftsin-derived peptides
Mechanism:
- GABAergic modulation — enhances GABA-A receptor function without direct binding (distinct from benzodiazepines)
- Serotonin metabolism — alters serotonergic turnover, increases 5-HT in cortical tissue
- IL-6 modulation — reduces IL-6 expression; contributes to anxiolytic and immune effects
- BDNF — mild elevation similar to Semax but not the primary mechanism
- Anxiolytic without sedation — preserves learning/memory unlike benzodiazepines
- Immune modulation — increases IgM, IgA, tuftsin-like phagocytosis activity
Typical research applications: generalized anxiety models (elevated plus maze, light/dark box), social-defeat stress, drug-withdrawal anxiety, PTSD models, immune-behavior crosstalk research.
Side-by-side comparison
| Property | Semax | Selank |
|---|---|---|
| Parent sequence | ACTH(4-7) | Tuftsin (4 aa) |
| Primary research use | Cognitive enhancement, neuroprotection | Anxiolysis, immune modulation |
| BDNF effect | Strong upregulation | Mild elevation |
| Neurotransmitter focus | Dopamine, serotonin, melanocortin | GABA, serotonin |
| Research model signature | Learning/memory, stroke | Anxiety, stress, immune |
| Sedation in models | No | No |
Administration in research
Both are often administered intranasally in research models — peptides penetrate the nasal mucosa and reach CNS via olfactory and trigeminal routes bypassing the blood-brain barrier. Subcutaneous and intraperitoneal administration also used.
Handling and quality
Both supplied as lyophilized powder. Typical research formats: 10 mg and 30 mg.
- Store lyophilized at -20°C, protected from light
- Reconstitute with sterile/bacteriostatic water
- Reconstituted stability ~4 weeks at 2–8°C
- Verify by HPLC (≥99.0%) with MS identity; request batch COA
- Intranasal formulations require sterile filtration
Related reading
- /research/semax — Semax compound profile
- /research/selank — Selank compound profile
- /compare/selank-vs-semax — direct mechanism comparison
- /category/cognitive-enhancement-research — broader category
RUO disclaimer
For laboratory research use only. Not intended to diagnose, treat, cure, or prevent any disease. Not for human consumption outside approved research settings.