How does it work?
In animal experiments, researchers see that Semax can affect the level of nerve growth factors in the brain, particularly a signalling substance called BDNF (brain-derived neurotrophic factor) and its receptor TrkB. These molecules are involved in how nerve cells grow, survive and form new connections. In models of oxygen deprivation (ischaemia), the peptide has also been studied for how it affects genes linked to inflammation and blood vessels. Exactly how Semax works in humans has still not been fully mapped.
Technical mechanism
ACTH(4-7) neuropeptide analogue. Increases BDNF and NGF levels, modulates dopaminergic and serotonergic systems, inhibits enkephalinase and angiotensin-converting enzymes.
What is being researched?
- Recovery and nerve function after ischaemic stroke (studies in humans and animals)
- BDNF and other nerve growth factors in the brain (mainly animal studies)
- Attention, short-term memory and the brain's resting-state network (smaller human studies)
- Nerve protection in oxygen deprivation and inflammation (animal models)
- Diseases of the optic nerve, including glaucoma (smaller clinical studies)
About the evidence: Much of the research on Semax comes from Russian research groups and is published in Russian. The human studies are usually small, and several lack randomisation and placebo control, which makes the results less robust. Most of the mechanistic knowledge is based on animal experiments (rats). Outside Russia, Semax has been little studied, and it is not approved as a medicine in most countries. The content here is intended for research purposes only.
Research profile
Studies and sources
The links go to independent research databases (PubMed, PubMed Central, ClinicalTrials.gov). The studies are in English and open in a new tab.
Ischaemic stroke and nerve protection
Semax has been investigated in animal models of stroke (oxygen deprivation) and in a clinical study of stroke patients. The animal experiments have explored how the peptide affects inflammation, blood vessels and nerve tissue after ischaemia.
- The efficacy of semax in the tretament of patients at different stages of ischemic stroke Clinical (human)PubMed· 2018
In this study of 110 patients after stroke (blood clot), the researchers investigated Semax. They measured a brain protein (BDNF), muscle function and the ability to carry out daily activities. Semax was given in courses via the nose. The patients who received Semax had higher levels of BDNF throughout the period, and both this and early rehabilitation were associated with faster improvement and a better outcome. The researchers believe early rehabilitation and Semax together may speed up recovery after stroke. Note that this is a Russian study.
- The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain PreclinicalPubMed· 2021
In this animal study in rats with artificially induced stroke, the researchers investigated Semax. The stroke increased the activity of several genes linked to inflammation. Semax dampened this increase, measured as lower levels of several inflammatory signals (including Il1a, Il1b and Il6). The researchers believe the protective effect of Semax in the stroke model may be due to the substance dampening inflammation. This is a Russian animal study, not a test in humans.
- Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats PreclinicalPubMed· 2017
In this animal study in rats with stroke, the researchers looked at which genes Semax and the fragment Pro-Gly-Pro (PGP) affect. They mapped the activity of many genes in the cerebral cortex. Semax particularly affected the immune response and increased the activity of genes linked to the immune system, while PGP appeared to dampen immune activity and signal transmission. The researchers suggest that Semax's protective effect may be related to the interplay between the nervous system and the immune system. This is a Russian animal study, not a test in humans.
- Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion PreclinicalPubMed· 2021
In this animal study in rats with stroke, the researchers examined proteins in the brain after treatment with Semax. They looked at proteins linked to inflammation and cell death (MMP-9, c-Fos, JNK) and to protection and rebuilding (CREB). One day after the stroke, there were signs of more active CREB and less of the inflammation and cell death proteins where Semax had been given. The researchers believe this supports Semax having a protective effect by dampening inflammation and cell death and promoting rebuilding. This is a Russian animal study.
- The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis PreclinicalPMC· 2014
In this animal study in rats with artificially induced stroke (a blood clot in a brain artery), the researchers mapped how Semax affects the activity of a very large number of genes in the cerebral cortex. Semax primarily increased the activity of genes linked to the immune system. Three hours after the stroke, Semax affected some genes that control immune cells, and after 24 hours the effect on the immune response was clearly greater. The researchers believe this may help explain how Semax has a protective effect after stroke. This is a Russian animal study, not a test in humans.
BDNF, neurotrophins and cognition
A large part of the research concerns how Semax affects nerve growth factors such as BDNF and NGF in the brain. These studies have mainly been done in rats, while a smaller human study has looked at the brain's resting-state network using fMRI.
- Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10 PreclinicalPubMed· 2007
In this animal study in rats, the researchers investigated how Semax affects genes for nerve growth factors. One hour after Semax was given in the nose, the activity of two such genes (NGF and BDNF) increased in the hippocampus, a memory area of the brain. BDNF also increased in the brainstem and cerebellum, while NGF decreased in the frontal lobe. The researchers conclude that Semax produces rapid and region-specific changes in these genes in the normal rat brain. This is a Russian animal study, not a test in humans.
- Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex PreclinicalPubMed· 2008
In this animal study in rats, the researchers followed how Semax affects two genes for nerve growth factors (BDNF and NGF) over time in the hippocampus and the frontal lobe. After a single dose in the nose, the activity changed rapidly: it fell in the hippocampus and rose in the frontal lobe after 20 minutes, returned to normal after 40 minutes, and then rose clearly after 90 minutes. The researchers describe a rapid, long-lasting and region-specific influence on these genes. This is an animal study, not a test in humans.
- Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action PreclinicalPubMed· 2010
In this animal study in rats, the researchers compared how Semax affects two genes for nerve growth factors (NGF and BDNF) over time in the hippocampus, the frontal lobe and the retina. The activity changed in different directions in the different areas. Shortly after the dose, activity fell in the hippocampus and the retina, but rose in the frontal lobe. In the retina, NGF remained fairly stable early on, while BDNF increased clearly after 90 minutes. This is an animal study, not a test in humans.
- Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia PreclinicalPMC· 2009
In this animal study in rats with artificially induced stroke, the researchers investigated how Semax and the fragment Pro-Gly-Pro (PGP) affect genes for nerve growth factors and their receptors in the cerebral cortex. Both substances increased the activity of several such genes, and the patterns partly overlapped. Semax increased BDNF, TrkC and TrkA, among others, three hours after the stroke, and NGF after 24 and 72 hours. The researchers showed for the first time that both Semax and PGP trigger the production of these nerve growth factors after stroke. This is a Russian animal study.
- Effects of Semax on the Default Mode Network of the Brain Clinical (human)PubMed· 2018
In this study of healthy volunteers (24 people), the researchers investigated Semax using brain scanning (fMRI) at rest. Participants were scanned before and 5 and 20 minutes after receiving Semax or a placebo in the nose. In the Semax group, the researchers saw a greater extent of a particular part of the brain's resting-state network (in the frontal area) compared with the control group. The researchers believe this confirms that Semax affects the brain's networks. This is a small Russian study in healthy people.
Optic nerve and eye health (human studies)
In some smaller Russian clinical studies, Semax has been investigated in patients with diseases of the optic nerve, including glaucoma. The studies are small and older, and should be interpreted with caution.
- Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone Clinical (human)PubMed· 2001
In this human study, Semax was used as part of nerve-protective treatment in patients with glaucoma in whom eye pressure had been normalised. The researchers used electrophysiological and computer-based examinations and reported that treatment with Semax had advantages compared with traditional nerve-protective treatment. They link this to the substance's nerve-protective and nerve-nourishing properties. This is a small Russian study, and the description is brief.
- Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease Clinical (human)PubMed· 2000
In this human study, Semax was given in addition to standard treatment to patients with various diseases of the optic nerve. The patients were divided into groups with different ways of giving the substance (nasal drops or electrophoresis) and a control group. The researchers reported that adding Semax had a beneficial effect on recovery, including better visual acuity, a larger visual field and better optic nerve function. This is a Russian study, and the description is relatively brief.