Semax — Nootropic neuropeptide — synthetic ACTH(4-7) analogue with C-terminal Pro-Gly-Pro extension (Russian Federation registered drug)
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH 4–7 sequence (MEHFPGP), which is the melanocortin receptor-inactive fragment of ACTH. The Pro-Gly-Pro C-terminal extension confers resistance to proteolytic degradation. Mechanisms: (1) Dramatically increases BDNF gene expression in hippocampus and prefrontal cortex — BDNF levels increase 1.4–1.7x within hours of intranasal administration (PMID: 29798983); (2) Upregulates NGF, GDNF, and NT-3 neurotrophin expression; (3) Inhibits pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in ischemic tissue; (4) Improves cerebral blood flow via NO modulation; (5) Activates HIF-1α-dependent gene expression during hypoxia, conferring neuroprotection. The net effect is enhanced synaptic plasticity, neurogenesis promotion, and neuroprotection against ischemic injury.
Overview
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Compound Class
Nootropic neuropeptide — synthetic ACTH(4-7) analogue with C-terminal Pro-Gly-Pro extension (Russian Federation registered drug)
Mechanism of Action
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH 4–7 sequence (MEHFPGP), which is the melanocortin receptor-inactive fragment of ACTH. The Pro-Gly-Pro C-terminal extension confers resistance to proteolytic degradation. Mechanisms: (1) Dramatically increases BDNF gene expression in hippocampus and prefrontal cortex — BDNF levels increase 1.4–1.7x within hours of intranasal administration (PMID: 29798983); (2) Upregulates NGF, GDNF, and NT-3 neurotrophin expression; (3) Inhibits pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in ischemic tissue; (4) Improves cerebral blood flow via NO modulation; (5) Activates HIF-1α-dependent gene expression during hypoxia, conferring neuroprotection. The net effect is enhanced synaptic plasticity, neurogenesis promotion, and neuroprotection against ischemic injury.
Regulatory Status
NOT FDA approved. NOT EMA approved. Registered as Rx drug in the Russian Federation for stroke and vascular cognitive impairment. Research peptide status in the US.
Evidence Level
C — Multiple Russian Phase 3 RCTs and prospective registries for stroke recovery and cognitive impairment (largest: n=110 stroke patients, BDNF increase confirmed, PMID: 29798983). No Western Phase 3 data; no FDA/EMA approval. Registered drug in Russia.