Semax

Semax is a seven-amino-acid peptide developed in the Soviet Union in the 1980s at the Institute of Molecular Genetics in Moscow. Its core is a fragment of ACTH — adrenocorticotropic hormone, the signal the pituitary sends to the adrenal glands — specifically residues 4 to 10, with three extra amino acids added to the end.

The reasoning behind it is the interesting part. ACTH had long been observed to affect learning and attention in animals independently of its hormonal function, which raised an obvious question: could the part responsible for the behavioural effect be separated from the part that drives the adrenal response? The 4–10 fragment does exactly that. It retains the central activity and has essentially no hormonal effect, because the region the adrenal receptor requires is not present.

The three residues added to the end — proline, glycine, proline — are a stability device rather than an active component. This tripeptide is itself a naturally occurring sequence that resists the enzymes which would otherwise dismantle a short peptide in minutes, and attaching it extends the working life of the molecule considerably. The same trick appears in other peptides from the same research tradition.

• Separating two functions of one hormone: It is a clear demonstration that the behavioural and hormonal activities of ACTH reside in different parts of the molecule. Questions of that kind are answered by exactly this sort of fragment.

• Neurotrophic factor expression: Published work reports increased expression of BDNF and NGF — proteins that keep neurons alive and support the formation of new connections. This is the most examined aspect of its mechanism.

• Stabilisation by a natural tripeptide: The Pro-Gly-Pro tail is a reusable design element from this research tradition, and studying it shows how a short peptide can be protected without changing what it does.

• A large but bounded literature: Decades of Russian clinical and laboratory work exist, much of it not replicated elsewhere. Understanding how to weigh that body of evidence is part of what makes this compound worth studying.

Neurons are not replaced readily, so the brain maintains the ones it has with a family of proteins called neurotrophic factors. Brain-derived neurotrophic factor, BDNF, is the best known: it keeps neurons alive, encourages new connections between them, and is required for the changes in connection strength that underlie learning. BDNF concentrations rise with exercise and fall under chronic stress.

Most published work on Semax concerns this system. Studies report increased expression of BDNF and of nerve growth factor in brain tissue after exposure, together with changes in the receptors those factors act on. The proposal is not that the peptide does anything directly to a neuron, but that it shifts the supply of the proteins maintaining the network.

How a short peptide produces that shift is not established. It has no well-characterised receptor of its own; suggestions include the melanocortin receptors its parent hormone acts on, and effects on the enzymes that break down neuropeptides. A well-documented downstream effect with an open question above it is a productive place for a research compound to sit, and it is where most current work on this peptide is aimed.

Semax is a registered medicine in Russia and has been studied there for decades, including in stroke and cognitive settings. That is a substantial body of work and it should not be dismissed. It should also not be read as equivalent to Western regulatory evidence: much of it is published in Russian, in journals with limited international reach, and by groups connected to the compound's development.

Independent replication outside the Russian tradition is limited, it holds no approval in the UK, EU or US, and it is supplied for laboratory research only. The neurotrophic findings are the best-supported part of its literature. Its research value is the separation it demonstrates: the behavioural activity of ACTH isolated from the hormonal, in a seven-residue peptide.

Selank comes from the same institute and uses the same Pro-Gly-Pro stabilising tail on a different core — a fragment of an immune peptide rather than of a hormone. The two are usually discussed together because their design logic is shared even though their targets are not.

Adamax is a modified version of this molecule with an added lipophilic cage, and Cerebrolysin approaches neurotrophic support from an entirely different direction — a mixture derived from brain tissue rather than a defined peptide.