Semax is a synthetic peptide derived from adrenocorticotropic hormone (ACTH) and is renowned for its cognitive-enhancing, neuroprotective, and immune-boosting effects. Originally developed in Russia, Semax has shown potential benefits in treating stroke, cognitive impairment, and neurodegenerative conditions.
Structure and Mechanism
- Peptide Sequence: Ac-Met-Glu-His-Phe-Pro-Gly-Pro
- Molecular Formula: C39H54N10O10S
- Molecular Weight: 854.99 g/mol
- PubChem CID: 122178 CAS: 80714-61-0
- Synonyms: Pro-Gly-Pro-ACTH
Primary actions
- BDNF & monoamines: Increases brain-derived neurotrophic factor (BDNF), dopamine, and serotonin.
- Gene expression: Modulates genes tied to memory, concentration, vascular/immune responses.
- Default mode network: Functional MRI suggests effects on the DMN (attention/arousal).
Key Benefits
- Cognitive enhancement: Improves learning, memory, attention; DMN effects.
- Stroke recovery: Supports neuron survival, mitochondrial stability, cerebral perfusion.
- Mood/anxiety support: May complement SSRIs by boosting BDNF; anxiolytic signals.
- Immune modulation: Alters cytokines/vascular gene programs.
- Neuroprotection: Broad protective effects in CNS models.
Research Highlights
- Stroke & neuroprotection: Faster functional recovery and higher BDNF during rehab.
- Gene expression: Rapid changes in hippocampus/frontal cortex (NGF/BDNF upregulation).
- Antidepressant potential: BDNF-linked mechanisms may accelerate SSRI response.
Suggested Use
- Nasal spray: 1 spray per nostril daily (protocols vary; clinician guidance advised).
Storage
- Frozen until first use; then refrigerate at 2–8 °C for up to 60 days.
What Is Semax?
Semax is a synthetic analogue of ACTH (amino acids 4–10 of ACTH) with added Pro-Gly-Pro for stability.
Semax Research (selected)
- Resting-state effects: DMN activity increases on fMRI [1,2].
- Stroke models/clinical rehab: Modulates ~24 vascular genes; improves neuronal survival and function; higher BDNF; better motor recovery [3,4].
- Hippocampus/cortex gene shifts: Single intranasal dose rapidly alters NGF/BDNF and other transcripts [5].
- Cognition: ACTH family protects learning/memory in epilepsy models; Semax posited to offer nootropic benefits [6].
- Depression: BDNF mediation offers a rationale to pair with SSRIs [7].
Mechanistic Theories
- Enzyme inhibition: Semax (and Selank) inhibit enkephalin-degrading enzymes, preserving endogenous peptides [6].
- Monoamine modulation: Elevates dopamine/serotonin; potential ADHD relevance [7].
- Immune/vascular genes: Broad remodeling of chemokine/immunoglobulin expression and vascular programs [8].
Potential Uses (preclinical/limited clinical)
- Neuroprotection; cognitive support; vascular protection (stroke/TBI contexts); ADHD hypotheses; stress/pain moderation.
Additional Studies & Trials (summarized)
- Nootropic properties: Rodent data show elevated 5-HIAA and striatal dopamine release; improved cognition indices [9].
- Neonatal SSRI model: Semax attenuated anxiety-like behavior and learning deficits after early fluvoxamine exposure [10].
- Post-MI vascular support: Improved LV remodeling metrics in rats post-infarct [11].
- Maternal deprivation model: Normalized anxiety/reactivity in adolescent rats after early deprivation [12].
- Ischemic stroke clinical study: Add-on Semax (12–18 mg over 5–10 days) improved neurological restoration vs. control therapy [13].
- Healthy volunteers (stress): Intranasal 0.015–0.050 mg/kg improved memory/attention at ~24h without notable adverse effects (small Russian trial) [14].
Safety, Dosing, Regulatory
- Side effects (reported): Generally well-tolerated in limited studies; peptide-class effects possible (injection-site irritation, dizziness, headache, nausea).
- Dose-response caveat: Low doses (5–50 µg/kg) showed antioxidant effects; high dose (450 µg/kg) increased oxidative stress in animals [15].
- Regulatory: Approved in Russia/Ukraine; not FDA-approved in the U.S. (research use only).
CompPharm Summary (as provided)
(Met-Glu-His-Phe-Pro-Gly-Pro) — Synthetic peptide (ACTH fragment + Pro-Gly-Pro).
Indications noted: stroke; memory/cognition disorders; peptic ulcers; depression/anxiety/sleep; age-related memory loss; immune boost; glaucomatous optic neuropathy.
Suggested dose: 1 spray per nostril daily.
Storage: Freeze until first use; then 60 days refrigerated at 2–8 °C.
Indications noted: stroke; memory/cognition disorders; peptic ulcers; depression/anxiety/sleep; age-related memory loss; immune boost; glaucomatous optic neuropathy.
Suggested dose: 1 spray per nostril daily.
Storage: Freeze until first use; then 60 days refrigerated at 2–8 °C.
References (exactly as you provided)
- A. Srivastava et al., Nootropic Phytomedicine. New Look to Phytomedicine, 2019. https://www.sciencedirect.com/topics/neuroscience/nootropic
- T. Kolomin et al., A New Generation of Drugs: Synthetic Peptides based on Natural Regulatory peptides. Neuroscience & Medicine, 2013, 223–252. http://dx.doi.org/10.4236/nm.2013.44035
- Dornbush RL, Nikolovski O. ACTH 4-10 and short-term memory. Pharmacol Biochem Behav. 1976;5(Suppl 1):69-72. https://pubmed.ncbi.nlm.nih.gov/189333/
- Essential Medicines and Health Products Information Portal, WHO resource.
- U.S. Food and Drug Administration, Drug databases.
- Kost NV et al. Bioorg Khim. 2001;27(3):180-3. https://pubmed.ncbi.nlm.nih.gov/11443939/
- Shih-Jen Tsai. Medical Hypotheses. 2007;68(5):1144-1146. https://doi.org/10.1016/j.mehy.2006.07.017
- Medvedeva EV et al. BMC Genomics. 2014;15:228. https://doi.org/10.1186/1471-2164-15-228
- Eremin KO et al. Neurochem Res. 2005;30(12):1493-500. doi:10.1007/s11064-005-8826-8
- Glazova NY et al. Neuropeptides. 2021;86:102114. https://doi.org/10.1016/j.npep.2020.102114
- Gavrilova SA et al. Ross Fiziol Zh. 2006;92(11):1305-21. https://pubmed.ncbi.nlm.nih.gov/17385423/
- Volodina MA et al. Bull Exp Biol Med. 2012;152(5):560-3. https://pubmed.ncbi.nlm.nih.gov/22803132/
- Gusev EI et al. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. https://pubmed.ncbi.nlm.nih.gov/11517472/
- Asmarin IP et al. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997;47(2):420-30. https://pubmed.ncbi.nlm.nih.gov/9173745/
- Bobyntsev I et al. Eksp Klin Farmakol. 2015;78(8):18-21. https://pubmed.ncbi.nlm.nih.gov/26591577/
