Semax is a drug which is used mostly in

Russia Russia (, , ), or the Russian Federation, is a List of transcontinental countries, transcontinental country spanning Eastern Europe and North Asia, Northern Asia. It is the List of countries and dependencies by area, largest country in the ...

and

Ukraine Ukraine ( uk, Україна, Ukraïna, ) is a country in Eastern Europe. It is the second-largest European country after Russia, which it borders to the east and northeast. Ukraine covers approximately . Prior to the ongoing Russian inv ...

for a broad range of conditions but predominantly for its purported

nootropic Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote re ...

neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...

, and neurorestorative properties. Semax has not been evaluated, approved for use, or marketed in most other countries.

Medical uses

Semax has undergone extensive study in Russia and is on the Russian ''List of Vital & Essential Drugs'' approved by the Russian Federation government on December 7, 2011. Medical uses for Semax include treatment of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

transient ischemic attack A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same Symptoms of stroke, symptoms associated with strokes, such as weakness or numbn ...

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...

and

cognitive disorder Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem solving. Neurocognitive disorders in ...

peptic ulcer Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...

optic nerve disease In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

, and to boost the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

Pharmacology

Pharmacodynamics

In animals, Semax rapidly elevates the levels and

expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...

brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...

(BDNF) and its signaling receptor

TrkB Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a recepto ...

in the

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, and rapidly activates

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

and

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...

brain systems. Accordingly, it has been found to produce

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

-like and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...

-like effects, attenuate the behavioral effects of exposure to

chronic stress Chronic stress is the physiological or psychological response induced by a long-term internal or external stressor. The stressor, either physically present or recollected, will produce the same effect and trigger a chronic stress response. There is ...

, and potentiate the locomotor activity produced by D-amphetamine. As such, it has been suggested that Semax may be effective in the treatment of depression. Though the exact

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

of Semax is unclear, there is evidence that it may act through

melanocortin receptor Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system each with differing specificities for melanocortins: * . MC1R is associate ...

s. Specifically, there is a report of Semax competitively antagonizing the action of the melanocortin receptor

full agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

α-melanocyte-stimulating hormone α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone and neuropeptide of the melanocortin family, with a tridecapeptide structure and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It ...

(α-MSH) at the MC₄ and MC₅ receptors in both ''in vitro'' and ''in vivo'' experimental conditions, indicating that it may act as an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

of these receptors. Semax did not antagonize α-MSH at the MC₃ receptor, though this receptor could still be a target of the drug. As for the MC₁ and MC₂ receptors, they were not assayed. In addition to actions at receptors, Semax, as well as a related peptide drug,

Selank Selank ( Russian: Cеланк) is a nootropic, anxiolytic peptide based drug developed by the Institute of Molecular Genetics of the Russian Academy of Sciences. Selank is a heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP). ...

, have been found to inhibit

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s involved in the degradation of

enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin ...

s and other

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

regulatory

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s ( IC₅₀ = 10 μM), though the clinical significance of this property is uncertain.

Pharmacokinetics

As a peptide, Semax has poor

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

and hence is administered

parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

ly as a

nasal spray Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for syste ...

or subcutaneous injection.

Human trials

In a 2018 study involving healthy participants, Semax was shown to increase

fMRI Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...

default mode network activity relative to placebo. In an earlier 1996 study, 250-1000 ug/kg of Semax improved attention and short term memory in healthy subjects performing 8 hour work shifts, though the effects were most pronounced when subjects were fatigued (after the shift was over) and the effects lasted going into the next day.Kaplan, A., Kochetova, A., Nezavibathko, V., Rjasina, T. and Ashmarin, I. (1996), Synthetic acth analogue semax displays nootropic-like activity in humans. Neurosci. Res. Comm., 19: 115-123. https://doi.org/10.1002/(SICI)1520-6769(199609)19:2<115::AID-NRC171>3.0.CO;2-B In the memory test administered the morning after Semax administration, the treatment group made more correct responses (71%) than the control group (41%). Both of the aforementioned studies had small sample sizes of 24 and 11 participants respectively. A study involving 110 patients recovering from ischemic stroke reported increases in BDNF (correlated with early rehabilitation) in patients administered Semax. As of September 2022, there are no published human trials involving Semax outside of Russia and

Post-Soviet The post-Soviet states, also known as the former Soviet Union (FSU), the former Soviet Republics and in Russia as the near abroad (russian: links=no, ближнее зарубежье, blizhneye zarubezhye), are the 15 sovereign states that wer ...

states.

Chemistry

Semax is a

heptapeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

and

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

analogue of a fragment of

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...

(ACTH), ACTH (4-10), of the following

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...

: Met-Glu-His-Phe-Pro-Gly-Pro ( in single-letter form).

References

{{Opioid receptor modulators Drugs with unknown mechanisms of action Enkephalinase inhibitors Melanocortin receptor antagonists Neuroprotective agents Peptides Russian drugs