7AA Approved (Russia) / Research (West)
Semax
Russia's approved stroke drug — ACTH-derived heptapeptide that floods the brain with BDNF and shields neurons from ischemic death.
In Plain English:
Semax is a synthetic 7-amino-acid peptide derived from ACTH(4-7), the adrenocorticotropic hormone fragment responsible for cognitive effects but stripped of all hormonal activity. Developed at the Institute of Molecular Genetics in Moscow, it has been approved in Russia since the early 1990s for ischemic stroke, cognitive impairment, and optic nerve disease. It dramatically upregulates BDNF and NGF, activates serotonergic and dopaminergic systems, and modulates the immune response in ischaemic tissue. Most Western users administer it intranasally for focus, memory, and neuroprotection.
Research Maturity
Approved (Russia) / Research (West) (228 results on PubMed for 'semax' (verified 2026-05-04)+ Studies)
Focus
Cognition
Mood / Stress
Neuroprotection
Origin
Synthesised at the Institute of Molecular Genetics, Russian Academy of Sciences, in the 1980s as an ACTH(4-7) analogue extended with Pro-Gly-Pro for metabolic stability. Listed on Russia's Vital and Essential Drugs list (decree 7 December 2011). Approved for ischemic stroke, cognitive disorders, optic nerve atrophy, and neurasthenia. Under FDA Pharmacy Compounding Advisory Committee review (scheduled July 24, 2026) for cerebral ischemia, migraine, and trigeminal neuralgia.
Mechanism
ACTH(4-7) core engages melanocortin receptors (MC1R–MC5R) and inhibits enkephalinase, prolonging endogenous opioid peptide activity. Single intranasal dose produces 1.4-fold increase in BDNF protein and 1.6-fold increase in TrkB phosphorylation in rat hippocampus. Upregulates NGF in multiple brain regions. Activates serotonin turnover (+25% 5-HIAA striatum; 180% extracellular 5-HT within 1-4 h) and potentiates dopaminergic signalling under stimulation. In ischaemia, alters expression of 164 genes across 3-24 h post-occlusion — predominantly immune (chemokines, immunoglobulins), vascular (endothelial, vasculogenesis), and anti-apoptotic pathways. Chelates Cu²⁺ ions, inhibiting Aβ:Cu²⁺ complex formation and retarding amyloid protofibril assembly. Active metabolite Pro-Gly-Pro provides independent neuroprotective actions.
Outcome
Russian clinical trial (N=110 stroke patients, PMID 29798983): early Semax administration elevated BDNF plasma levels throughout study, accelerated Barthel Index recovery, and improved motor performance vs control. Genome-wide analysis in rat pMCAO model (PMID 24661604): altered 164 ischaemia-related genes, identifying immunomodulation and vascular stabilisation as primary neuroprotective mechanisms. Alzheimer's mouse model (PMID 41479572, 2025): 2.8-fold cortical amyloid plaque reduction at 7.5 months; effect persisted 1.5 months post-treatment. ACTH dopamine/serotonin study (PMID 16362768): semax activated striatal serotonergic system and dramatically enhanced amphetamine-induced dopamine effects, consistent with monoamine facilitation.
