Semax

Overview

Semax is a synthetic heptapeptide derived from the N-terminal fragment (4-10) of adrenocorticotropic hormone (ACTH). It was originally developed in Russia, where it has been studied and clinically used for decades. That distinguishes it from many other peptides in this database that are still entirely in the preclinical phase.

The most consistently demonstrated effect of Semax in research is the stimulation of BDNF (Brain-Derived Neurotrophic Factor). BDNF is a protein essential for the growth, survival, and adaptation of nerve cells. Multiple independent studies show that Semax, administered intranasally, increases BDNF levels in specific brain regions such as the hippocampus and the basal forebrain.

In Russia, Semax is registered by the authorities for use in ischemic stroke and in optic nerve disorders, and it appears on the Russian list of vital and essential medicines. Several human clinical studies exist; some used a control group or placebo comparison, and one is classified in the literature as randomised. These studies are small, originate almost entirely from a single Russian research tradition, and do not meet the scale and methodology of large international phase III trials. The existence of human intervention data is scientifically relevant; the limited size and the absence of independent replication are equally so.

As with many compounds in this field, the evidence base is concentrated in specific research groups and regions, and large randomised controlled studies are lacking. The findings are scientifically grounded, but independent international replication is needed to consolidate them.

Mechanism of action

Semax centres on one key protein: BDNF. It works like a growth factor for nerve cells: it keeps them healthy and helps them form new connections. Semax switches on the production of BDNF, mainly in two brain regions that matter for memory and attention: the hippocampus and the basal forebrain.

BDNF stimulation

• Binds with high affinity to specific receptors in the basal forebrain (KD ≈ 2.4 nM)
• Rapidly increases BDNF protein levels after intranasal administration in the hippocampus and basal forebrain
• Simultaneously stimulates activation of trkB (the primary BDNF receptor), which amplifies the signalling cascade

Neurotrophin gene expression

• Increases BDNF gene expression in the hippocampus, brainstem, and cerebellum
• Increases NGF (Nerve Growth Factor) gene expression in the hippocampus
• Region-specific effects: not all brain regions respond equally

Monoamine and behavioural effects

• Normalises biogenic amine levels in animal models after chemical disruption
• Reduces anxiety-related behaviour in stress models
• Improves learning and memory performance in conditioned-avoidance models

Research findings

• In animal studies, intranasal Semax increases BDNF protein levels in the hippocampus and basal forebrain, a finding replicated across multiple independent groups
• In a clinical study of 110 stroke patients (non-randomised), Semax increased plasma BDNF levels and was associated with an improved Barthel index
• In a resting-state fMRI study in 52 healthy participants, changes in the functional connectivity of the amygdala were measured after administration of Semax
• In animal models, Semax improved learning and memory performance consistently with intranasal administration
• Semax is registered by the authorities in Russia for ischemic stroke and cognitive disorders, reflecting the maturity of the Russian clinical research programme

In-vitro and molecular findings

• Specific receptor binding in the basal forebrain (KD ≈ 2.4 nM)
• Rapid upregulation of BDNF and trkB mRNA in hippocampal and glial cell cultures
• Protection of neuronal and endothelial cells against copper-induced toxicity

Animal-model findings

• Increased BDNF levels in the hippocampus, basal forebrain, brainstem, and cerebellum
• Improved cognitive performance in conditioned-avoidance and maze models
• Normalisation of circadian rhythm and locomotor activity after chronic administration
• Reduced anxiety and improved learning capacity after early-neonatal pharmacological disruption

Human findings

• In a clinical study of 110 stroke patients, Semax raised plasma BDNF levels and was associated with an improved Barthel index, a measure of self-sufficiency (Gusev 2018). The study had no randomised placebo control.
• In two earlier controlled clinical studies, Semax was investigated in acute ischemic stroke (30 patients with a control group of 80) and in optic nerve disorders (with a control group and different routes of administration); both reported favourable effects on recovery.
• In a study classified as randomised, in 27 patients with motor neuron disease, Semax improved reported quality of life, but did not alter the course of the disease itself.
• In a resting-state fMRI study in 52 healthy participants, with a placebo comparison, changes in the functional connectivity of the amygdala were measured after administration of Semax.
• Semax is registered in Russia for stroke rehabilitation and optic nerve disorders and appears on the national list of essential medicines.
• Detection in smuggled pharmaceutical preparations in Europe (Sciensano, Belgium) points to use outside a clinical or research context.

Research context

The Russian registration programme includes human intervention data in stroke patients, a serious starting point. Some of these studies used a control group or placebo comparison, and one is classified in the literature as randomised. Even so, they originate almost entirely from a single research tradition, are small in design, and broad international replication is absent. Large randomised studies to modern international standards have not been published.

BDNF stimulation is the most solidly demonstrated effect of Semax and offers a plausible biological mechanism for the reported cognitive effects. BDNF plays a central role in synaptic plasticity, the brain's capacity to adapt. That mechanism is widely studied in the context of neurodegenerative disorders.

An honest point in the profile: Semax has been detected in smuggled preparations in Europe (Sciensano, Belgium, 2020). The same analysis notes that Semax and Selank have not completed clinical trials to Western standards. This underlines the importance of a careful, informed approach and of verifiable provenance.

Open questions

The clinical registration in Russia and the availability of human intervention data make Semax a comparatively richer research subject than many peptides at earlier stages. Independent international replication remains necessary to consolidate the findings scientifically.

• Large randomised controlled trials to international standards are lacking; the available clinical work is small in design and largely confined to a single research tradition
• The optimal dose and administration frequency for different applications have not been established
• The long-term safety profile in humans has not been systematically studied
• The mechanism of action in humans has not been directly confirmed; the BDNF data come primarily from animal models
• Interaction with existing medication in neurological patients is insufficiently studied
• Independent international replication of the clinical findings is scarce

Research outlook

Independent international clinical studies, ideally randomised and controlled, to validate the Russian findings

BDNF modulation as a research mechanism is of broad scientific interest; Semax is an interesting study model within that field

Research into its role in neurodegenerative disorders such as Alzheimer's and Parkinson's

Further development of analytical methods for detection in biological matrices, relevant to doping and forensic research

Scientific interest

BDNF expression and synaptic plasticity

Neuroprotection in ischemic brain injury

Cognitive function and learning capacity

Neurotrophin signalling in ageing

Specifications

References

1. [Effectiveness of semax in acute period of hemispheric ischemic stroke]. · Gusev EI, Skvortsova VI, Miasoedov NF, et al. · Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova · 1997
2. [Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease]. · Polunin GS, Nurieva SM, Baiandin DL, et al. · Vestnik Oftalmologii · 2000
3. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. · Shadrina MI, Dolotov OV, Grivennikov IA, et al. · Neuroscience Letters · 2001
4. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. · Dolotov OV, Karpenko EA, Seredenina TS, et al. · Journal of Neurochemistry · 2006
5. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. · Dolotov OV, Karpenko EA, Inozemtseva LS, et al. · Brain Research · 2006
6. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10. · Agapova TY, Agniullin YV, Shadrina MI, et al. · Neuroscience Letters · 2007
7. [Chronic partial denervation and quality of life in patients with motor neuron disease treated with semax]. · Serdiuk AV, Levitskii GN, Miasoedov NF, Skvortsova VI. · Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova · 2007
8. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity. · Tabbì G, Magrì A, Giuffrida A, et al. · Journal of Inorganic Biochemistry · 2014
9. The efficacy of semax in the treatment of patients at different stages of ischemic stroke. · Gusev EI, Martynov MY, Kostenko EV, et al. · Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova · 2018
10. Functional Connectomic Approach to Studying Selank and Semax Effects. · Panikratova YR, Vlasova RM, Akhutina TV, Korneev AA, Sinitsyn VE, Pechenkova EV · Dokl Biol Sci · 2020
11. The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations. · Vanhee C, Francotte A, Janvier S, Deconinck E. · Drug Testing and Analysis · 2020
12. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats. · Glazova NY, Manchenko DM, Volodina MA, et al. · Neuropeptides · 2021

Availability

In stock · Batch PEP-SEM-2025-01 · HPLC 99.37 % · released 21 Jun 2026

• Semax 10 mg · product page with price and batch CoA