Semax

In simple words

Semax is a Russian peptide drug based on a fragment of a pituitary hormone; it is given as nose drops. It is studied as a way to protect the brain after a stroke and to improve attention and memory.

What this molecule is

ACTH(4-10)-Pro-Gly-Pro: Met-Glu-His-Phe-Arg-Trp-Gly-Pro-Gly-Pro. 10 aa. ~1000 Da. IMG RAS; registered in Russia and Ukraine.

Why it is studied

A registered nootropic and neuroprotective drug. Clinical data: acute ischemic stroke (reduced neurological deficit), ADHD, cognitive improvement in healthy people. Hippocampal BDNF ↑ 1.4-2× within 1 hour. 30+ years of clinical use in Russia.

How it works

↑BDNF and TrkB receptors in the hippocampus and cortex → neuroplasticity. ↑dopaminergic (D1/D2) and serotonergic systems → attention, memory, motivation. ↓TLR4/NF-κB → ↓neuroinflammation. Pro-Gly-Pro tail: ↑stability + its own neuroprotective effect (enkephalin-like).

Doses used in studies

Studies used intranasal administration (Semax 0.1%, 1 drop ≈ 50 mcg) at 200-600 mcg/day (4-12 drops), 1-2 times/day, for a course of 5-14 days. In acute stroke, Semax 1% was used intranasally at 12-18 mg/day for 5 days.

Combined with in studies

• Selank — dopamine + enkephalin: a daytime duo
• DSIP — sleep: in the evening
• Cerebrolysin — neurogenesis + neuroprotection
• Noopept

Level of evidence

Level B Human observational data. There are studies in humans, but they are small, uncontrolled, or cohort studies. The data are encouraging but need confirmation. Registered drug in Russia; clinical data in stroke. Nootropic effects: clinical case series.

Important to know

⚠️ Intranasal administration: alternate between nostrils. Effect: concentration and motivation within 30-60 min. Evening use is possible (does not interfere with sleep).

Studies in PubMed

1. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. (Brain Res, 2006)
2. [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. (Zh Nevrol Psikhiatr Im S S Korsakova, 2018)
3. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress. (Eur J Pharmacol, 2024)
4. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats. (Neuropeptides, 2021)
5. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. (Neurochem Res, 2005)
6. The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease. (Acta Naturae, 2025)