# Semax

Semax is a medication which is used in Russia and Eastern Europe for the treatment of a broad range of conditions like brain trauma but predominantly for its claimed nootropic, neuroprotective, and neurorestorative effects.
The mechanism of action of Semax is unknown. It might interact with certain melanocortin receptors or inhibit enkephalinase enzymes. Chemically, Semax is a peptide and a synthetic analogue of a fragment of adrenocorticotropic hormone (ACTH).
Semax was first described by 1991. Although used as a prescription drug in Russia and Eastern Europe, Semax has not been evaluated, approved for use, or marketed in most other countries. The drug is widely sold by online vendors and used as a purported nootropic (cognitive enhancer).

## 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, transient ischemic attack, memory and cognitive disorders, peptic ulcers, optic nerve disease, and to boost the immune system.

### Clinical trials

In a 1996 study, 250 to 1000 μg Semax improved attention and short-term memory in 11 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. In a follow-up memory test administered the morning after Semax administration, the treatment group made more correct responses (71%) than the control group (41%).
A 2018 study involving 110 patients recovering from ischemic stroke reported increases in brain-derived neurotrophic factor (BDNF) (correlated with early rehabilitation) in patients administered Semax.
In another 2018 study involving 24 healthy participants, Semax was shown to increase fMRI default mode network activity relative to placebo.
As of November 2023, there are no published clinical trials involving Semax outside of Russia and post-Soviet states.

## Pharmacology
### Pharmacodynamics

In animals, Semax rapidly elevates the levels and expression of brain-derived neurotrophic factor (BDNF) and its signaling receptor tropomyosin receptor kinase B (TrkB) in the hippocampus, and rapidly activates serotonergic and dopaminergic brain systems. Accordingly, it has been found to produce antidepressant-like and anxiolytic-like effects, attenuate the behavioral effects of exposure to chronic stress, 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 of Semax is unclear, there is evidence that it may act through melanocortin receptors. Specifically, there is a report of Semax competitively antagonizing the action of the melanocortin receptor full agonist α-melanocyte-stimulating hormone (α-MSH) at the MC$_4$ and MC$_5$ receptors in both in vitro and in vivo experimental conditions, indicating that it may act as an antagonist or partial agonist of these receptors. Semax did not antagonize α-MSH at the MC$_3$ receptor, though this receptor could still be a target of the drug. As for the MC$_1$ and MC$_2$ receptors, they were not assayed. In addition to actions at receptors, Semax, as well as a related peptide drug, Selank, have been found to inhibit enzymes involved in the degradation of enkephalins and other endogenous regulatory peptides (IC$_{50}$ = 10 μM), though the clinical significance of this property is uncertain.

### Pharmacokinetics

As a peptide, Semax has poor oral bioavailability and hence is administered parenterally as a nasal spray or subcutaneous injection.

## Chemistry

Semax is a heptapeptide and synthetic analogue of a fragment of adrenocorticotropic hormone (ACTH), ACTH (4-10), of the following amino acid sequence: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP in single-letter form).

## History

Semax was first described in the scientific literature by 1991.

## Society and culture
### Etymology

Semax is composed of seven amino acid residues: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), which is reflected in the name - from an abbreviation of "seven amino acids"—in Russian: СЕМь АминоКиСлот—СЕМАКС.

### Marketing

Semax was developed, produced, and marketed by Peptogen in the Russian Federation with participation of the Institute of Molecular Genetics of the Russian Academy of Sciences.