Semax

Semax (MEHFPGP) is a synthetic heptapeptide analog of ACTH(4-10) developed at the Institute of Molecular Genetics in Moscow, designed to provide neuroprotective and cognitive-enhancing effects without the endocrine side effects of native ACTH. The Pro-Gly-Pro C-terminal extension stabilizes the peptide against proteolytic degradation and significantly extends its half-life compared to the parent ACTH fragment. Semax's primary neuroprotective mechanism involves robust upregulation of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB in the hippocampus, cerebral cortex, and striatum — a key pathway for neuronal survival, synaptic plasticity, and long-term potentiation. A single intranasal dose of Semax (6000 mcg) produces a maximal 1.4-fold increase in hippocampal BDNF protein and 1.6-fold increase in TrkB phosphorylation within 20 minutes, with effects persisting for several hours. This rapid BDNF induction is accompanied by CREB (cAMP response element-binding protein) phosphorylation and activation of immediate early genes involved in synaptic strengthening. Additionally, Semax modulates dopaminergic and serotonergic neurotransmitter systems, enhancing attention, working memory, and learning capacity in animal models and human trials. It also reduces NF-κB activation and pro-inflammatory cytokine production, contributing to its neuroprotective profile in ischemic and neurotoxic injury models. Semax is authorized in Russia and Ukraine as a clinical drug for acute ischemic stroke, encephalopathy, optic nerve atrophy, and cognitive impairment. Clinical studies confirm improved neurological outcomes, motor recovery, and BDNF-mediated rehabilitation benefits in stroke patients. Current research investigates applications in Alzheimer's disease (reducing amyloid-β aggregation and tau pathology), Parkinson's disease, ADHD, and traumatic brain injury recovery.