Semax
Nootropic / Neuroprotective Peptideapproved_foreignAlso known as: ACTH(4-7)-PGP, Heptapeptide Semax, MEHFPGP
A synthetic heptapeptide derived from ACTH(4-10) with a Pro-Gly-Pro C-terminal extension, used as a nootropic and neuroprotectant with regulatory approval in Russia for stroke and cognitive disorders.
Overview
Semax is a synthetic peptide analogue of the adrenocorticotropic hormone (ACTH) fragment 4-7, with an added Pro-Gly-Pro tripeptide at the C-terminus that enhances its stability and biological activity. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s, Semax has been approved in Russia and several CIS countries since 2011 for the treatment of stroke, transient ischemic attacks, cognitive disorders, peptic ulcers, and optic nerve diseases. Unlike full-length ACTH, Semax does not stimulate the adrenal cortex and has no hormonal activity. Its primary effects are nootropic (cognitive enhancement), neuroprotective, and neurotrophic. Semax increases brain-derived neurotrophic factor (BDNF) expression, modulates serotonergic and dopaminergic systems, and has demonstrated anti-inflammatory and immunomodulatory properties. It is typically administered intranasally, providing convenient non-injection delivery with rapid CNS effects.
Mechanism of Action
Semax exerts its effects through multiple neurological pathways: (1) Increases expression of BDNF and its receptor TrkB, promoting neuronal survival, growth, and synaptic plasticity; (2) Modulates the serotonergic system by influencing tryptophan hydroxylase and serotonin metabolism; (3) Enhances dopaminergic neurotransmission, contributing to improved focus and motivation; (4) Activates the melanocortin system (MC3R/MC4R) without adrenocortical stimulation; (5) Suppresses inflammatory cytokines and modulates immune responses in the CNS; (6) Increases expression of neurotrophins NGF and NT-3; (7) The Pro-Gly-Pro extension inhibits degradation by prolyl endopeptidases, extending half-life significantly compared to native ACTH fragments; (8) Modulates gene expression related to the immune and vascular systems in the brain.
Molecular Formula
C37H51N9O10S
Molecular Weight
813.93 g/mol
Sequence
Met-Glu-His-Phe-Pro-Gly-Pro
Dosage Protocols
Dose Range
200mcg – 600mcg
Frequency
2-3 times daily
Route
intranasal
Cycle Length
10-20 days, with breaks of equal duration
Standard Russian clinical dosing uses 0.1% solution, 2-3 drops per nostril. Total daily dose typically 600-900mcg. Cycle on/off to prevent tolerance.
Source: Russian clinical protocols and prescribing information
Side Effects
| Effect | Severity |
|---|---|
| Nasal irritation | mild |
| Headache | mild |
| Hair shedding | mild |
| Emotional changes | mild |
| Dizziness | mild |
Pros & Cons
Approved medication in Russia with decades of clinical use and a well-documented safety profile
Intranasal administration is convenient and non-invasive, with rapid CNS delivery
Increases BDNF, one of the most important neurotrophic factors for brain health and plasticity
No hormonal (adrenocortical) activity despite being derived from ACTH
Very mild side effect profile with minimal reports of adverse effects
Most clinical research is published in Russian-language journals, limiting Western peer review
Not FDA-approved, with limited large-scale Western clinical trials
Cycling is recommended to prevent tolerance development
Research chemical sources may have variable quality and purity
Research Studies
Legal Status
Approved in Russia and several CIS countries as a prescription medication. Not FDA-approved. Available as a research chemical in the US and Europe. Not specifically scheduled in most Western countries.
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