Semax research: what the published studies show

Binding and BDNF in Rat Brain

A 2006 study found that cell membranes from rat basal forebrain contain binding sites for Semax, and binding of the tritium-labeled peptide was time dependent, specific, reversible and calcium-requiring.^[1] The dissociation constant was 2.4 plus or minus 1.0 nanomolar and the maximum binding capacity 33.5 plus or minus 7.9 femtomoles per milligram of protein.^[1]

The same study gave Semax intranasally at 50 and 250 micrograms per kilogram, and BDNF protein rose in the basal forebrain three hours later.^[1] It did not rise in the cerebellum.^[1] That null makes it a regional finding, not a whole-brain one.^[1]

The authors write that the cognitive effects of Semax might be associated, at least in part, with the increased BDNF protein.^[1] Both hedges are theirs.^[1]

Neurotrophin Expression in Glial Culture

A 2001 study treated glial cells from the basal forebrain of newborn rats with Semax, and BDNF messenger RNA rose eightfold while NGF messenger RNA rose fivefold.^[2] The largest increase came at 30 minutes.^[2]

This is in vitro work in one primary cell population.^[2] It measures messenger RNA rather than protein, and says nothing about an intact animal.^[2]

Penetration and Degradation

A 2006 study labeled Semax with tritium at the C-terminal proline and gave it intranasally to rats at 50 micrograms per kilogram.^[3] Two minutes later, 0.093 percent of the administered radioactivity per gram was present in brain, and eighty percent of that belonged to intact Semax.^[3]

The peptide undergoes rapid enzymatic degradation, and the tripeptide Pro-Gly-Pro predominates in biological samples relative to the total of parent compound and metabolites.^[3] Anyone reading a downstream effect as an effect of the intact heptapeptide should weigh that, because most of what reaches tissue is not the intact heptapeptide.^[3]

Nitric Oxide After Global Ischemia

A 2001 study induced incomplete global ischemia in Wistar rats by occluding both common carotid arteries.^[5] Nitric oxide production doubled and secondary products of lipid peroxidation rose moderately, and nitric oxide content in brain correlated with the degree of neurological disturbance.^[5] Semax at 0.3 milligrams per kilogram prevented both the neurological disturbance and the excess nitric oxide in cortex.^[5]

A companion paper tested glycine alongside Semax in the same model.^[4] Glycine did not reduce nitric oxide levels and did not improve the neurological deficits, while Semax reduced the nitric oxide rise and restored neurological functioning.^[4]

These two papers are not independent replications. They share four authors, one model and one year, in two journals.^[4]Together they are one result reported twice.^[5]

Human Studies

A 1997 study gave Semax to 30 patients in the acute period of hemispheric ischemic stroke, against 80 controls.^[7]Assessment used EEG with mapping and repeated somatosensory evoked potentials, and the authors report that including Semax had some influence on the rate of restoration of neurological function.^[7] Doses were 12 milligrams in moderate strokes and 18 in severe ones.^[7]

A 2018 study followed 110 patients after ischemic stroke.^[6] They were 43 men and 67 women, mean age 58.0 plus or minus 9.7 years.^[6] Patients were split into early and late rehabilitation groups, each subdivided into those receiving Semax and those not.^[6] The regimen was two 10-day courses at 6,000 micrograms daily.^[6]

Plasma BDNF, motor performance on the Medical Research Council scale and the Barthel index were measured.^[6] High plasma BDNF correlated with early rehabilitation, and Semax with higher BDNF correlated with faster improvement and a better final Barthel score.^[6] The reported results are correlations and the abstract describes no randomization or blinding.^[6]

State of the Evidence

The evidence gets weaker as it gets closer to people.^[1] The cell and rat work reports defined endpoints in named models, including a binding constant and a regional null.^[2] The human work is two studies from one lead investigator, neither of them described as randomized or blinded.^[6]

Authorship is concentrated.^[3] Three Moscow groups account for all seven references.^[3] References 1 and 2 share an author.^[2] References 4 and 5 are one group reporting a single model twice, and references 6 and 7 share a first author across twenty-one years.^[5] No group unconnected to this program has replicated any of it in the retrieved record.^[4]

The degradation result shapes how the rest should be read, because most of what is recoverable from tissue shortly after dosing is the Pro-Gly-Pro fragment.^[3] No source here separates an effect of the parent from an effect of that fragment.^[1]

Nothing here describes what the compound does in a healthy person, because both human studies enrolled patients after ischemic stroke.^[7]