What doses were studied — and in what models?

What these dose numbers mean

Semax has never been formally evaluated in large Western randomized controlled trials. Every dose figure on this page comes from animal research — rats and mice, measured in micrograms per kilogram — or from the Russian regulatory record. These are not human dosing recommendations.

The dose ranges are narrow and consistent across independent labs: 50 microg/kg intranasal for neurotrophin and memory studies, 100 microg/kg intraperitoneal for stroke/ischemia work, and roughly 60 nmol/kg in a 2024 chronic-stress study. Consistency matters because it allows cross-study comparison — but the route matters equally, and intraperitoneal injection (the dominant research route) does not translate directly to intranasal use in humans.

The most useful pharmacokinetic fact: after an intranasal dose in rats, intact Semax reaches brain tissue within two minutes but converts to the PGP metabolite within one hour. Measurable biological effects like BDNF elevation persist 20 to 24 hours despite this rapid clearance — a dissociation between the peptide's half-life and its downstream effects that remains incompletely explained.

Research context: what this page covers

Semax is not FDA-approved and has not been evaluated in large-scale human clinical trials published in Western peer-reviewed journals. All dosage data summarized here comes from rodent models and, where noted, the Russian regulatory record. This page describes what was studied in research settings — doses, routes, timing, and study outcomes — not what doses are safe or appropriate for human use. No recommendation is made or implied.

For human clinical application, the appropriate reference is a licensed clinician familiar with the applicable regulatory environment.

Doses studied in the animal research literature

The Semax literature uses a narrow, consistent range of doses across independent research groups, which makes cross-study comparison reasonably tractable.

Research Dose 01 — 50 microg/kg intranasal (rat and mouse models): This is the primary dose used in neurotrophin induction studies and in the Alzheimer's-model research. Dolotov 2006 used this dose intranasally to demonstrate BDNF protein elevation in rat basal forebrain within three hours ^[1]. Agapova 2007 used the same dose intranasally to document BDNF and NGF mRNA upregulation in hippocampus, brainstem, and cerebellum within one hour ^[2]. Radchenko 2025 used 50 microg/kg intranasal every other day for one month in transgenic Alzheimer's-model mice, demonstrating 2.8-fold amyloid plaque reduction ^[11]. The pharmacokinetic study by Shevchenko 2006 also used 50 microg/kg intranasal with radiolabeled Semax, confirming brain penetration within two minutes ^[13].

Research Dose 02 — 100 microg/kg intraperitoneal (rat stroke/ischemia models): This is the dominant dose in the stroke neuroprotection literature. Dmitrieva 2009 used 100 microg/kg IP in permanent MCAO rats ^[3]; Sudarkina 2021 used it in a 90-minute tMCAO model ^[4]; Medvedeva 2014 used it in focal cerebral ischemia ^[5]; Filippenkov 2020 and 2023 both used approximately 100 microg/kg IP in tMCAO protocols ^[6][7]. The consistency across independent research groups using this dose in the same model type strengthens its status as the representative research dose for the neuroprotection literature.

Research Dose 03 — 60 nmol/kg daily intraperitoneal (chronic stress model): Inozemtseva 2024 used 60 nmol/kg daily IP in a chronic unpredictable stress model in male Sprague-Dawley rats over a multi-week period ^[10]. Converting to mass units: at a molecular weight of 887.0 Da, 60 nmol/kg corresponds to approximately 53 microg/kg — closely aligned with the neurotrophin-induction dose range used intranasally.

Research Dose 04 — 50 microg/kg intranasal, developmental window (neonatal isolation model): Volodina 2012 administered 50 microg/kg intranasal during postnatal days 15-28 in a neonatal isolation model, documenting lasting normalization of adrenocortical and glycemic regulation ^[14].

Research Dose 05 — 20-100 micromolar (in vitro): Sciacca 2022 used 20-100 micromolar concentrations in vitro for amyloid-beta copper-chelation studies ^[9]. In vitro molar concentrations do not translate directly to in vivo dosing.

Routes of administration studied

Intranasal: The primary route in the clinical registration (Russian Federation intranasal 0.1% formulation) and in the neurotrophin, cognitive, and Alzheimer's-model studies. The pharmacokinetic data for this route is the most detailed: Shevchenko 2006 confirmed brain penetration within two minutes of intranasal administration at 50 microg/kg in rats, with approximately 80% intact peptide detectable at the two-minute mark ^[13].

Intraperitoneal: The dominant route in the stroke/ischemia rodent literature. IP delivery provides rapid systemic distribution and is used for timed protocols (e.g., at occlusion, 1.5 h, and 5 h post-reperfusion) ^[4]. IP data does not directly extrapolate to human intranasal use.

Intravenous: Referenced in the Russian regulatory literature for acute stroke protocols ^[15]. No detailed IV pharmacokinetic data is available in the Western indexed literature.

Half-life and pharmacokinetic profile

Semax is a small peptide and subject to enzymatic degradation. The C-terminal Pro-Gly-Pro tripeptide was incorporated specifically to confer peptidase resistance relative to the parent ACTH(4-7) tetrapeptide — a structural solution to a practical stability problem ^[13].

The radiolabeled pharmacokinetic study provides the clearest available data: after intranasal administration at 50 microg/kg in rats, intact Semax was detectable in brain tissue at two minutes (approximately 80% intact). By one hour, the Pro-Gly-Pro (PGP) metabolite had become the predominant species in brain tissue, indicating rapid enzymatic conversion within the brain itself ^[13].

Despite this rapid peptide clearance, biological effects — measurable BDNF protein elevation, neurotrophin mRNA changes — persist for 20-24 hours ^[1][13]. This dissociation between parent compound half-life and biological effect duration is consistent with receptor-mediated downstream signaling: the peptide binds and initiates a cascade that outlasts the peptide's presence. The PGP metabolite may also contribute independently, as it has been studied separately for anti-inflammatory and neuroprotective properties ^[3].

Systemic half-life data for the intranasal route in humans is not available in the reviewed Western peer-reviewed literature.

Human clinical data: Russian regulatory context

Semax has been registered as a pharmaceutical in the Russian Federation since the 1990s, approved for ischemic stroke and cognitive impairment as an intranasal 0.1% formulation ^[15]. The Russian registration safety profile describes no CNS depression, no cardiovascular toxicity, no drug dependence, and no withdrawal syndrome ^[15].

This registration constitutes the primary source of formal human-use data for Semax. However, the underlying clinical trial data, dose-response studies, and RCTs informing the Russian registration are largely published in Russian-language journals not indexed in PubMed or Medline, and have not been independently replicated in large Western RCTs. The Western peer-reviewed evidence base for Semax is robust at the rodent and in vitro level but thin at the human clinical level.

For these reasons, all dosage information on this page is framed as research context only. Semax is not approved for human use outside the Russian Federation. Its regulatory status in the United States, European Union, United Kingdom, and most other jurisdictions is unresolved.