Semax

Semax (C37H51N9O10S, 813.9 g/mol) was developed by researchers at the Institute of Molecular Genetics of the Russian Academy of Sciences and Moscow State University. Its first four residues, Met-Glu-His-Phe, are positions 4 to 7 of ACTH, a stretch known to influence attention and memory in animals. Because this short fragment is degraded quickly, a Pro-Gly-Pro tail was added, which slows enzymatic breakdown and prolongs activity. Semax is often described in the literature as an ACTH(4-10) analogue.

Crucially, the ACTH(4-7) core carries none of ACTH's hormonal activity: Semax does not stimulate the adrenal glands to release cortisol. Its effects are on the nervous system, which is why it has been developed as a nootropic and neuroprotective agent. Semax is registered as a medicine in Russia, where it is used in stroke and cognitive disorders, but it is not authorised anywhere in the EU.

The best-documented mechanism is neurotrophic. In rodent brain, Semax rapidly increases BDNF, the growth factor that supports neuron survival, synapse formation and memory consolidation, and activates its receptor TrkB. Research also points to effects on immune and vascular gene networks after brain ischaemia and to inhibition of the enzymes that degrade enkephalins.

Benefits of Semax reported in research

The key mechanistic study is Dolotov et al. (Brain Research, 2006). A single application of Semax in rats produced a maximal 1.4-fold rise in hippocampal BDNF protein, a 1.6-fold rise in TrkB tyrosine phosphorylation, and 3-fold and 2-fold rises in exon III BDNF and TrkB mRNA. Treated rats also performed better in conditioned avoidance learning. A companion paper the same year in the Journal of Neurochemistry showed that Semax binds specifically in the rat basal forebrain and increases BDNF protein there within hours, and a 2003 study had already found BDNF upregulation across several brain regions.

Stroke research forms the second pillar. Using permanent middle cerebral artery occlusion in rats, Medvedeva et al. (BMC Genomics, 2014) ran a genome-wide transcriptional analysis of ischaemic cortex. Semax predominantly enhanced immune-related genes, particularly immunoglobulins and chemokines, and altered 24 vascular-system genes at 3 hours and 12 at 24 hours after occlusion, pointing to effects on inflammation control and blood-vessel repair in damaged tissue. Later proteomic work in ischaemia-reperfusion models reported a consistent protective profile.

Human data come from Russia, where Semax is a registered medicine. Gusev et al. (2018) followed 110 patients in early and late rehabilitation after ischaemic stroke. Patients who received Semax had plasma BDNF levels that rose and stayed high throughout the study, and showed faster motor recovery and better final Barthel index scores than those who did not. These are open clinical studies rather than large blinded trials, so they rank below Western regulatory evidence, but they agree well with the animal BDNF data.