# Semax Dosage Research Context — Preclinical Doses, Russian Approved Labeling, Pharmacokinetics > The Semax dosage record from the published literature: preclinical microgram-per-kilogram ranges in rats, Russian approved-label milligram-per-day intranasal regimens, half-life, and the Pro-Gly-Pro metabolite. Research context only. What the published Semax literature documents about doses, routes, durations, and pharmacokinetics. This is a research summary, not clinical guidance — Semax is not FDA-approved and cannot be lawfully prescribed in the United States. ## SECTION 01 / DOSAGE IN PLAIN TERMS Semax dosage in the published literature falls into two categories: rodent preclinical figures (expressed as micrograms per kilogram, used in mechanism and neuroprotection studies) and Russian approved-label clinical figures (expressed in milligrams per day, used in the ischemic stroke and optic-nerve-disease trials). Neither category constitutes a human-dose recommendation for the United States or any jurisdiction where Semax is not an approved medicine. **Semax is not FDA-approved.** The preclinical and clinical figures documented on this page are research-context values from cited investigators, not prescribing labels. The Russian approved-label doses were derived through formal Russian clinical trials; they cannot be lawfully filled at a US pharmacy because no FDA-recognized labeling exists for Semax. ## SECTION 01 / PRECLINICAL DOSES In the rat preclinical literature, Semax has been administered most commonly via the intranasal route at single doses between 50 and 250 mcg/kg, or via the intraperitoneal route at 60 nmol/kg to 100 mcg/kg in ischemia and chronic-stress models. The Dolotov 2006 hippocampal `BDNF`/`TrkB` study used 50 mcg/kg intranasally in male Wistar rats and reported the canonical 1.4-fold `BDNF` protein increase and 1.6-fold `TrkB` phosphorylation increase three hours after a single dose [1]. The companion binding study extended the dose range to 250 mcg/kg intranasally and identified specific basal-forebrain binding with `Kd` of 2.4 nM [2]. In the rat transient `MCAO` ischemia model, 100 mcg/kg intraperitoneally is the working dose across the Sudarkina 2021 protein-expression study [4], the Dmitrieva 2009 neurotrophin transcription study [5], and the Medvedeva 2014 genome-wide `RNA-Seq` study [6]. Romanova and colleagues used 50 mcg/kg intranasally daily for six days in the focal photoinduced ischemia model [7]. Inozemtseva and colleagues in the 2024 chronic unpredictable stress depression model used 60 nmol/kg intraperitoneally — substantially lower than the ischemia doses [10]. These figures are research-context values reported by the cited investigators. They are not human-dose recommendations. Allometric scaling between rat and human routinely overstates equivalent human doses; the published clinical doses in the Russian approved labeling were derived through formal clinical trials, not back-calculated from rodent work. ## SECTION 02 / RUSSIAN APPROVED LABELING The Russian Federation's prescribing register documents two Semax formulations and two principal indication groups. For acute ischemic stroke, Semax 1% intranasal is dosed at 12 mg/day for moderate strokes over a five-day course and up to 18 mg/day for severe strokes over a ten-day course [3]. For the recovery phase after ischemic stroke, the Gusev recovery-phase study used 6,000 mcg/day (6 mg/day) intranasal Semax in two ten-day courses separated by a twenty-day interval [14]. The pediatric indication for minimal brain dysfunction uses Semax 0.1% — two drops in each nostril three times daily for twenty days, with two to four courses per year. For glaucomatous optic neuropathy, the Polunin study used Semax 0.1% intranasal as an adjunct to standard topical intraocular-pressure-lowering therapy [15]. These figures are documented in the Russian-language prescribing information and in the Russian clinical literature. They are not approved labeling in the United States, European Union, United Kingdom, or Canada — no marketing authorization exists in those jurisdictions, and the Russian approved-label doses cannot be lawfully filled at a US pharmacy because no FDA-recognized labeling exists. ## SECTION 03 / PHARMACOKINETICS The intact Semax peptide has a remarkably short plasma half-life — Shevchenko and colleagues, working with radiolabeled tracer doses in rats, measured a parent-peptide plasma half-life of two to five minutes after intranasal administration [13]. Yet the functional effects of a single dose persist substantially longer: `BDNF` and `NGF` mRNA upregulation and enkephalinase inhibition continue for twelve to twenty-four hours after dosing. The resolution to this apparent paradox is the active metabolite `Pro-Gly-Pro`. The terminal `PGP` tripeptide is cleaved from the parent heptapeptide and is itself biologically active — it accumulates in central nervous system tissue with a much longer functional residence time than the intact peptide. Dmitrieva and colleagues demonstrated that `PGP` administered alone activates the same neurotrophin and neurotrophin-receptor gene programs in damaged cortex as the parent peptide, though with less spatial selectivity to injured tissue [5]. Approximately 0.093% of an intranasal Semax dose enters brain tissue within two minutes of administration via the olfactory and trigeminal nose-to-brain transport pathways [13]. This rapid CNS penetration is the pharmacokinetic rationale for the intranasal route in the Russian clinical protocols — peripheral systemic exposure to the intact peptide is brief, but the CNS exposure to the parent peptide and its `PGP` metabolite is what carries the functional effect. ## SECTION 04 / STABILITY AND ROUTE NOTES The C-terminal `Pro-Gly-Pro` extension is the structural feature that distinguishes Semax from native `ACTH(4-7)`. The `PGP` tail shields the parent fragment from rapid aminopeptidase degradation, extending biological activity at the cost of a slower onset relative to the intact `ACTH` fragment. The same structural choice is what makes the intranasal route practical — without `PGP` protection, the intact `ACTH(4-7)` fragment would be cleaved before it reached the central nervous system in functionally meaningful amounts. General peptide-handling guidance for the lyophilized compound calls for storage at 2 to 8 °C. Reconstituted solution should be refrigerated and protected from light per the same general guidance. The Russian-approved 0.1% and 1% intranasal formulations are commercial finished products with their own stability and storage specifications documented in the Russian prescribing information; those specifications do not apply to laboratory-reagent material sold in the United States, which is supplied as lyophilized powder for in-vitro use only and is not certified for human administration. Routes studied in the published literature include intranasal (the primary clinical route — preserves olfactory and trigeminal nose-to-brain transport), intraperitoneal (preclinical only — used across the Sudarkina 2021 [4], Dmitrieva 2010 [5], Medvedeva 2014 [6], and Inozemtseva 2024 [10] studies), subcutaneous (preclinical and some research-protocol use), and in vitro for the enkephalinase, copper-chelation, and calcium-dynamics studies [9][12][17]. Oral administration is not a route reported in the indexed Semax literature; like most short peptides, intact Semax is expected to be degraded by gastric and intestinal proteases before reaching systemic circulation. ## SECTION 05 / COURSE STRUCTURE IN THE RUSSIAN LITERATURE The Russian clinical record uses a course-based dosing structure rather than continuous daily administration. The acute ischemic stroke protocol is five days at 12 mg/day for moderate strokes or ten days at 18 mg/day for severe strokes [3]. The recovery-phase protocol used by the Gusev recovery-phase study runs two ten-day courses of 6,000 mcg/day separated by a twenty-day interval [14]. The pediatric minimal-brain-dysfunction protocol uses twenty-day courses at two drops of 0.1% in each nostril three times daily, repeated two to four times per year. The course-and-interval structure is a pharmacological pattern rather than a marketing convention — the Russian-language pharmacology literature on related regulatory peptides (including Selank) uses similar intermittent dosing across courses. The published rationale rests on the persistence of `BDNF` and `NGF` gene-expression effects beyond the duration of plasma drug exposure [1][8] and on the accumulation of the `PGP` metabolite in central nervous system tissue [13]. Whether this course structure is necessary for the observed clinical effects or whether continuous daily dosing would produce equivalent outcomes has not been tested in a published head-to-head trial. For preclinical investigators planning research protocols, the most commonly replicated dose-route combinations are 50 mcg/kg intranasal single-dose for `BDNF` and `TrkB` upregulation studies in rats [1][2], 100 mcg/kg intraperitoneal single-dose for `MCAO` ischemia outcome studies [4][6], and 60 nmol/kg intraperitoneal daily for chronic-stress depression models [10]. These are the historical reference doses against which new preclinical work calibrates. --- An indexed editorial digest of peer-reviewed Semax research — not a clinic, not a pharmacy, not a prescription.