Semax
A Russian ACTH(4-10)-derived nootropic that acts through neurotrophins, not the adrenal axis.
Identity
- Class
- Synthetic heptapeptide — ACTH(4-7) extended with Pro-Gly-Pro
- Source
- Synthetic; based on the melanocortin fragment ACTH(4-10)
- Receptor
- No classical melanocortin-receptor role; drives BDNF/neurotrophin signaling centrally
Key properties
Approximate values for the native hormone. Engineered analogs are often deliberately larger and far longer-acting.
Mechanism
Semax is an engineered fragment of ACTH(4-10) — the melanocortin sequence stripped of its cortisol-releasing hormone activity and capped with a C-terminal Pro-Gly-Pro that resists peptidase cleavage. Rather than acting as a melanocortin hormone, it upregulates BDNF and its receptor TrkB and shifts dopaminergic and serotonergic tone, the basis of the nootropic and neuroprotective effects studied largely in Russian programs, where it is a registered drug.
Reference notes
- It keeps the neuroactive core of ACTH(4-10) while shedding the steroidogenic hormone activity — a fragment repurposed away from its parent's endocrine role.
- Its central effects run through BDNF/TrkB and monoamine systems, not the melanocortin receptors.
- Registered and used clinically in Russia; independent Western trial evidence remains limited.
Selected literature
Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.
- 1.Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents · Neurochemical research, 2005 · PMID 16362768
- 2.Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia · Cellular and molecular neurobiology, 2010 · PMID 19633950
- 3.Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats · Neuropeptides, 2021 · PMID 33418449