PPK-V versus Cortexin, Semax and Dalargin: rat peptide-profile study
E. B. Shustov, D. Yu. Ivkin, A. S. Ivkina, A. E. Kim, S. L. Lublin, M. S. Nesterov · 2020 · Search for the optimal mass profile of neuropeptides for the implementation of antihypoxic and activating actions. Pharmacy Formulas. 2020;2(4):72–81.
Related evidence maps: Sports performance ↗
Reported findings and study design
Reported findings
Raw times and standardized T-scores are shown separately below. Larger reported values are not a dose-matched estimate of superiority.
Ten rats per group; males for chamber hypoxia (time to agonal signs) and females for loaded swimming (time to exhaustion). Single rectal exposure one hour before testing; saline vehicle controls. Separately performed experiments were standardized and pooled.
Dose, route and schedule
Single rectal administration one hour before testing. Methods list Dalargin 0.56 mg/kg, Semax 0.22 mg/kg, Cortexin 1 mg/kg and experimental peptide preparations 2.5 mg/kg. Combination components were not dose-reduced. The discussion instead gives an overall range up to 8.06 mg/kg for PPK-E; this discrepancy is unresolved.
Protocol source ↗ · Original methods and dose-analysis discussion; animal protocol, not human dosing
| Measure | Result | Comparison, timing and statistics |
|---|---|---|
| PPK-V: hypoxia time | 552±44 s; Cortexin 201±11 s; displayed control 95±3 s | Table 2, M±m; separate experiments and unequal doses; no verified pairwise PPK-V-versus-Cortexin p-value |
| PPK-V: loaded-swimming time | 289±66 s; Cortexin 172±44 s; displayed control 135±6 s | Table 2, M±m; 10% body-weight load; female cohort differs from the male hypoxia cohort |
| Route, timing and nominal PPK dose | Rectal, once, one hour before testing; experimental preparations 2.5 mg/kg in methods | Discussion maximum: 8.06 mg/kg for PPK-E; individual complex exposures not fully reconciled |
| Cortexin alone | Hypoxia 201±11 s; loaded swimming 172±44 s | Displayed controls 95±3 s and 135±6 s; M±m; methods dose 1 mg/kg rectally |
| Semax alone | Hypoxia 218±23 s; loaded swimming 221±60 s | Displayed controls 95±3 s and 135±6 s; M±m; methods dose 0.22 mg/kg rectally |
| Dalargin alone | Hypoxia 170±8 s; loaded swimming 201±12 s | Displayed controls 95±3 s and 135±6 s; M±m; methods dose 0.56 mg/kg rectally |
| Combination comparisons | Cortexin + Dalargin: 250±15 s / 275±62 s; Semax + Dalargin: 293±25 s / 198±10 s | Hypoxia / swimming; M±m. Components were not dose-reduced. The combined Semax/Dalargin swimming mean was below Semax alone (221±60 s); no formal synergy demonstrated. |
| 5–10 kDa fraction and hypoxia | D=0.44; p=10⁻²⁰ | Table 5 pooled factor analysis; association does not identify the active molecule or establish causation |
| 5–10 kDa fraction and swimming | D=0.01; p=0.97 | Table 6: no association detected in this analysis; the hypoxia finding is not a general performance result |
| Dose as a confounding factor | Reported dose-factor D=0.31 for hypoxia and D=0.40 for swimming | Table 4; composition and exposure varied together. The authors grouped doses across different preparations. |
| Mass-profile reporting gap | PPK-V fractions total 95.33%; Cortexin fractions total 98.37% | Calculated sums of Table 1 entries, not new laboratory results. Final bin heading >1 kDa conflicts with the narrative <1 kDa; no renormalization. |
| Safety and duration | No dedicated adverse-event counts, long-term follow-up or human PPK-V outcome supplied | An acute functional assay cannot establish a safe human regimen |
Table 2: raw times and T-scores kept separate
| Preparation | Hypoxia time (s), M±m | Hypoxia T-score, M±m | Swimming time (s), M±m | Swimming T-score, M±m |
|---|---|---|---|---|
| Saline control | 95±3 | 50±1 | 135±6 | 50±2 |
| Dalargin | 170±8 | 79±3 | 201±12 | 331±38 |
| Semax | 218±23 | 97±9 | 221±60 | 397±198 |
| Cortexin | 201±11 | 91±4 | 172±44 | 235±143 |
| Cortexin + Dalargin | 250±15 | 110±5 | 275±62 | 576±202 |
| Semax + Dalargin | 293±25 | 126±10 | 198±10 | 319±33 |
| PPK-A · hippocampus | 532±47 | 418±128 | 309±71 | 684±233 |
| PPK-B · brainstem | 538±23 | 418±73 | 186±27 | 280±90 |
| PPK-V · cortex | 552±44 | 460±130 | 289±66 | 621±215 |
| PPK-G · combined regions | 551±46 | 456±135 | 373±95 | 896±311 |
| PPK-D · combined regions | 498±30 | 298±87 | 369±92 | 886±300 |
| PPK-E · combined regions | 487±22 | 267±67 | 344±61 | 800±200 |
Original Table 2, p.76; matching 2019 monograph Table 110, p.296, visually inspected. n=10 per experimental group; separate sex-specific endpoint cohorts. Hypoxia time ends at agonal signs, not long-term survival; swimming time ends at exhaustion. Source M±m notation retained. Experiment-specific control normalization means T-score percentages are not raw-time improvements. No pairwise superiority p-values supplied here.
Table 1: reported mass-bin fractions
| Preparation | 10–30 kDa (%) | 5–10 kDa (%) | 1–5 kDa (%) | Final bin (%) |
|---|---|---|---|---|
| Dalargin | — | — | — | 98 |
| Semax | — | — | — | 100 |
| Cortexin | — | 33.37 | 62 | 3 |
| Cortexin + Dalargin | — | 5 | 18 | 77 |
| Semax + Dalargin | — | — | 75.55 | 24 |
| PPK-A | 14.88 | 38.73 | 39.11 | 4.77 |
| PPK-B | 2.54 | 43.5 | 49.04 | 4.92 |
| PPK-V | 11.39 | 35.39 | 43.15 | 5.4 |
| PPK-G | 30 | 36.27 | 25.51 | 5.58 |
| PPK-D | 13.83 | 25.63 | 23.54 | 35.48 |
| PPK-E | 12.7 | 20.23 | 48.87 | 18.2 |
Original Table 1, p.76; matching monograph Table 109, p.295, visually inspected. Final heading is printed >1 kDa, although the narrative describes <1 kDa; unresolved source inconsistency. — means a blank source cell, not verified zero. Fractions are not forced to total 100%. Molecular-mass bins do not identify peptide sequences or brain uptake.
This is a composition–activity hypothesis from pooled animal experiments. PPK-V is a distinct experimental cortex hydrolysate, not Cortexin or the brainstem PPK-B. Unequal exposures, source inconsistencies and matching earlier tables limit comparisons. No clinical superiority, formal combination synergy or intranasal PPK-V delivery has been established.
Source for the extracted data ↗ · Checked 2026-11-08
What the PPK-V comparison establishes
PPK-V (ППК «В») is the cortex-derived experimental mixture in Shustov and colleagues’ 2020 paper. PPK-B (ППК «Б») comes from brainstem. These letter codes identify different preparations. Their composition is not established as equivalent to commercial Cortexin.
The related experimental preparations
| Code | Original label | Tissue source |
|---|---|---|
| PPK-A | ППК «А» | Hippocampus |
| PPK-B | ППК «Б» | Brainstem |
| PPK-V | ППК «В» | Cerebral cortex |
| PPK-G | ППК «Г» | Combined brain regions; exact formulation unresolved |
| PPK-D | ППК «Д» | Combined brain regions; exact formulation unresolved |
| PPK-E | ППК «Е» | Combined brain regions; exact formulation unresolved |
“Analogue” here describes a related research preparation. It does not establish a shared active sequence, potency, manufacturing process or interchangeable clinical product. See the PPK research card ↗.
Why the raw values do not prove superiority
The paper pools separately performed experiments and transforms their observations to T-scores using experiment-specific controls. Hypoxia and swimming were also measured in different sexes. The displayed control values therefore should not be treated as a verified shared concurrent control for every row.
A T-score is a shifted, standardized value: T = 50 + 10Z. Its zero is arbitrary. A ratio or percentage of T-scores is not a proportional change in seconds, exercise capacity or clinical benefit. No preparation-specific pairwise test establishes that PPK-V is superior to Cortexin.
The preparations also received unequal doses. Methods give 2.5 mg/kg for experimental complexes, but the discussion describes a maximum of 8.06 mg/kg for PPK-E. The study does not reconcile every complex’s actual exposure, so an apparent potency ratio would be unreliable. Combining two drugs without reducing component doses also does not demonstrate pharmacological synergy.
What 5–10 kDa means
This is a molecular-mass range of 5,000–10,000 daltons. Using an approximate average of 110 daltons per amino-acid residue gives roughly 45–90 residues for a simple peptide; this is an illustration, not sequence identification. A mixture’s chromatography bin can contain different molecules.
The reported fraction association concerns hypoxia resistance. The swimming analysis for the same bin was neutral. PPK-V and Cortexin also had similar reported 5–10 kDa fractions, despite different outcome means. The fraction alone cannot explain their difference or establish a generally optimal human peptide size.
Rectal administration is not evidence of nose-to-brain delivery
This experiment used one rectal exposure an hour before testing. It measured functional outcomes, not intact-peptide concentrations in brain, nasal absorption or blood–brain-barrier transport. Molecular mass by itself cannot establish delivery by another route.
Two distinct Cortexin sources provide context: a 2011 rat seizure study used intranasal nanoparticles or intraperitoneal solution and reported both neutral acute and favorable chronic findings; a 2002 human report combined nasal Cortexin with sensory/vestibular training. Neither establishes intranasal PPK-V delivery, and the human abstract does not isolate the drug’s contribution.
The 2019 book contains matching data
Pages 295–296 of Work Capacity, Fatigue, Correction contain Tables 109–110 with the same mass fractions and outcome values as Tables 1–2 of the 2020 article. The recovered book pages were visually inspected. These are linked reports from one research program, rather than independent replication.
The journal’s indexed full text was checked, but its PDF page images could not be retrieved. Visual table checking used the recovered monograph. The public links point to the original journal article ↗ and the book’s author-upload record ↗.
What would resolve the remaining questions?
Priority gaps are preparation-specific dose records, original experiment identifiers and controls, matched-exposure replication, sequence and batch characterization, and route-specific pharmacokinetics. No adverse-event denominator or long-term PPK-V safety program is established by this acute study.
Molekul summary of the linked publication. Educational information, not medical advice. Seek qualified healthcare help for medical conditions.
Methods, limitations & source review
Study limitations
- Different-sex cohorts and separate experiments contributed to the two endpoints; randomization is stated, but masking, allocation concealment and complete animal flow are not established.
- Doses were unequal, and the nominal experimental-preparation dose in methods conflicts with the discussion maximum. Table 2 does not resolve each complex’s actual exposure.
- Table 2 reports M±m; its uncertainty notation is retained without relabeling it as a verified SD. No preparation-specific pairwise p-values or confidence intervals establish PPK-V superiority over Cortexin.
- T-scores standardize results against experiment-specific controls. Their percentages and ratios cannot be interpreted as proportional increases in raw swim time or clinical performance.
- Table 1’s final bin is printed >1 kDa, while the narrative describes <1 kDa. Some fractions do not sum to 100%; blank cells are not assumed zero and values are not renormalized.
- The 5–10 kDa association is observational within the pooled analysis, not isolation of an active sequence or proof of brain penetration. Rectal results do not establish intranasal delivery.
- Matching 2019 and 2020 numerical tables are treated as one research program. No human PPK-V efficacy or long-term safety follows from these results.
Publication counts are not counts of independent trials. Reviews, translations and reports sharing participants may overlap. Findings apply to the studied preparation, population and endpoints.
Document format: Original publisher indexed HTML/PDF text; matching tables in recovered 2019 monograph
Review depth: Original indexed methods and Tables 1–7 checked; matching monograph pp.294–296 visually inspected. Original journal PDF page images not recovered.
Related-report group: shustov-brain-peptide-profiles-2019-2020. Reports in this group are not assumed to be independent trials.
Source access and review scope
Expanded from a qualitative listing using original publisher indexed full text. Table 2 outcome values and Table 1 profiles match the recovered 2019 book, Tables 110 and 109, pp.295–296. The book is retained privately; it is not a separate replication. Original journal page images could not be retrieved.
Recorded source-check date: 2026-11-08. This date does not imply a completed systematic review.
Source type: Original animal and analytical journal research
Open original source or index record ↗
DOI: 10.17816/phf52964
Citation and original source
Original source: E. B. Shustov, D. Yu. Ivkin, A. S. Ivkina, A. E. Kim, S. L. Lublin, M. S. Nesterov. PPK-V versus Cortexin, Semax and Dalargin: rat peptide-profile study Search for the optimal mass profile of neuropeptides for the implementation of antihypoxic and activating actions. Pharmacy Formulas. 2020;2(4):72–81. 2020.
Molekul research summary: https://molekul.io/research/shustov-neuropeptide-profiles-2020. Cite the original publication for its findings and this page when referring to Molekul’s summary or evidence appraisal.
Bibliography entryRelated compound profiles
PPK-V & brain peptide complexes
A collection of experimental calf-brain peptide mixtures, including cortex-derived PPK-V and distinct hippocampal, brainstem and combined-region preparations. Rat performance and hypoxia experiments do not establish equivalence to Cortexin.
Cortexin
A tissue-derived preparation with Russian stroke, cognitive, pediatric and other clinical reports. Study designs vary; the independent stroke review is shown alongside favorable original reports. None validates the personal WHOOP diary.
Semax
ACTH-fragment-derived peptide with clinical stroke and optic-nerve reports, healthy-volunteer imaging and preclinical neuroregulation research. Precursor, patent and dissertation sources remain separately labeled.
Dalargin
A Soviet synthetic opioid hexapeptide investigated in cytoprotection, stress, hypoxia, ischemia and trauma. Its enkephalin lineage is distinct from organ-derived peptide bioregulators; historical proposals and laboratory effects are not established clinical indications.