Semax has something almost no other research peptide sold in spray format has: a published intranasal pharmacokinetic study with a real number attached, using radiolabelled compound in a live animal. The number is smaller than people expect, and the study that produced it also documents how quickly the peptide falls apart. Both halves belong in any honest account of the route.
The molecule
Semax is a heptapeptide corresponding to the ACTH(4-10) fragment with a Pro-Gly-Pro tail: Met-Glu-His-Phe-Pro-Gly-Pro. The parent fragment is an adrenocorticotropic hormone sequence stripped of hormonal activity; the C-terminal extension is the same stabilising modification used in Selank, added to slow enzymatic breakdown of a short peptide that would otherwise be destroyed almost immediately in plasma.
The intranasal measurement
Shevchenko and colleagues published the study in 2006. They prepared a Semax analogue tritium-labelled at the C-terminal proline with a molar radioactivity of 56 Ci/mmol, administered it intranasally to white rats of 200-250 g at 50 µg/kg in 20 µl of solution, and tracked where it went.
Two minutes after administration, 0.093 percent of the total administered radioactivity per gram was present in rat brain. Of that radioactivity, 80 percent was intact Semax and the remainder was metabolites.
Both figures matter and they pull in different directions. The two-minute timepoint establishes that the nose-to-brain route is fast. This is not a slow systemic accumulation, it is direct access on a timescale that systemic absorption and barrier crossing could not produce. The 0.093 percent per gram establishes that the delivered fraction is small. And the 80 percent intact figure means that what arrived arrived mostly as Semax rather than as fragments, which is the more favourable of the two possible readings.
The same paper is blunt about the other half: the peptide undergoes rapid enzymatic degradation, with the tripeptide Pro-Gly-Pro predominating in biological samples relative to total Semax and metabolite content. The stabilising tail slows degradation; it does not prevent it, and it becomes the dominant breakdown product itself.
The corroborating work
Sheremet and colleagues reported in 2004 that tritium-labelled Semax administered intranasally penetrated both brain and eyes in rats, in work aimed at optic nerve applications. Independent labelling, same route, same qualitative conclusion.
Zolotarev and colleagues in 2006 characterised Semax degradation in the presence of nerve cells, identifying the pentapeptide HFPGP and the tripeptide PGP as major products, and separately reported that Semax inhibits blood plasma enkephalinases through action on aminopeptidases. That last finding is interesting on its own terms (the peptide interferes with the enzymes that degrade other peptides) but it is a plasma observation, not a route comparison.
What is absent
No published study administers Semax intranasally and parenterally in the same model and compares brain exposure. The intranasal figure above has no injected counterpart to be measured against, so the comparison cannot be quantified in either direction.
The rodent limit is also unusually relevant here. The 0.093 percent per gram figure was obtained in animals whose olfactory epithelium occupies a far larger proportion of the nasal cavity than a human's does, and the olfactory surface is precisely the structure the direct pathway uses. That number should be read as evidence the pathway exists and operates quickly, not as a human delivery fraction.
The takeaway
Semax is among the best-characterised research peptides for intranasal delivery, and the characterisation is one radiolabelled rat study plus corroboration: 0.093 percent of administered radioactivity per gram of brain at two minutes, 80 percent of it intact peptide, against rapid degradation to Pro-Gly-Pro. Fast access, small fraction, short life. No injected comparison has been published. We stock Semax as a nasal spray and as a lyophilised vial, and this is one of the few compounds where a protocol can cite an actual intranasal number rather than an assumption.
All products are intended for research use only. Not for human consumption. Must be 21 years of age or older to purchase.
References
1. Shevchenko, K. V., Nagaev, I. Yu., Alfeeva, L. Yu., et al. (2006). Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration. Bioorganicheskaia Khimiia, 32(1), 64-70. https://doi.org/10.1134/s1068162006010055
2. Sheremet, N. L., Polunin, G. S., Ovchinnikov, A. N., et al. (2004). An experimental substantiation for using the "Semax" neuroprotector in the treatment of optic-nerve diseases. Vestnik Oftalmologii, 120(6), 25-27.
3. Zolotarev, Yu. A., Dadaian, A. K., Dolotov, O. V., et al. (2006). Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation. Bioorganicheskaia Khimiia, 32(2), 183-191.
