What Is Semax?

Overview

Semax is a synthetic heptapeptide built around the ACTH(4-7) fragment with a Pro-Gly-Pro tail added for stability, giving the sequence Met-Glu-His-Phe-Pro-Gly-Pro (molecular formula C₃₇H₅₁N₉O₁₀S). It originated from research into short adrenocorticotropic-hormone fragments, but it was deliberately constructed to retain the neuroactive portion of ACTH while shedding the hormone's classic corticotropic activity. In research it is studied chiefly as a neuropeptide that influences central-nervous-system biology rather than as an endocrine agent.

How Semax Works

The leading mechanistic account centres on neurotrophic signalling: in laboratory models Semax raises expression of brain-derived neurotrophic factor (BDNF) and its trkB receptor, particularly in hippocampal and basal-forebrain tissue. Beyond that pathway, studies describe modulation of dopaminergic and serotonergic transmission and shifts in gene-expression programs tied to immune response and vascular function. It is often discussed in the context of the melanocortin-receptor family, the receptors its parent hormone acts on, though the peptide itself lacks the hormonal output of ACTH. The full mechanism is not considered settled, and the available work does not establish that any single signalling effect translates into a defined functional outcome.

What the Research Explores

• BDNF/trkB neurotrophic signalling and changes in plasma BDNF after treatment.
• Neuroprotection in ischemic-stroke and focal-ischemia models, including acute and rehabilitation contexts.
• Cognitive and nootropic endpoints such as attention, memory and default-mode-network activity on functional imaging.
• Dopamine and serotonin system activation in pre-clinical work.
• Gene-expression responses spanning immune-response and vascular pathways after focal ischemia.

Forms & Handling

In the published literature Semax is most often administered intranasally — an intranasal 1% solution was used in a neuroimaging protocol — with injectable formats appearing in experimental settings. For laboratory work it is typically supplied as a lyophilized powder reconstituted with bacteriostatic or sterile water and kept refrigerated once in solution. Working concentration is simply the amount of peptide divided by the final liquid volume; intranasal versus injectable routes differ in absorption, so bioavailability is hard to generalise across formats. See the dosing protocols below for the reconstitution math expressed in insulin-syringe units.

Safety & Research Notes

Semax is an investigational research compound with no U.S. FDA-approved prescribing label. U.S. regulators have flagged compounded Semax preparations as a safety concern, citing potential immunogenicity, aggregation, peptide-related impurities and limited safety data for the proposed routes. Reported effects in the human literature are mostly route-specific, such as nasal irritation and headache, but limited reported harm is not evidence of safety: long-term effects, interactions with CNS-active medications and behaviour in neurologic-disease populations remain insufficiently characterised. Anything described here is mechanistic background, not a usage recommendation.

References

Related Protocols