Semax

Cognitive Enhancement & Neuroplasticity

• Improves learning speed, attention, and short-term memory in healthy individuals and stress-impaired models.
• Enhances memory retention and recall in preclinical behavioral tests (e.g., novel object recognition, passive avoidance).
• Stimulates synaptic plasticity and long-term potentiation through BDNF/TrkB signaling.
• Supports hippocampal and cortical remodeling, promoting cognitive resilience.

Mood Regulation & Stress Recovery

• Reduces anxiety-like and depression-like behaviors in chronic stress and early-life adversity models.
• Normalizes serotonergic and dopaminergic neurotransmission in mood-related brain regions.
• Potentiates antidepressant effects of monoaminergic stimulation without causing sedation.
• Improves behavioral response to unpredictable stress, supporting emotional stability.

Neuroprotection & Stroke Recovery

• Preserves brain tissue in ischemic models by reducing infarct volume and limiting neuron loss.
• Accelerates neurological rehabilitation and functional independence in human stroke patients.
• Upregulates BDNF, NGF, and growth-related genes for neuronal regeneration.
• Protects neurons from oxidative, hypoxic, and excitotoxic injury in vitro and in vivo.

Neurotransmitter Modulation

• Increases serotonin availability and stabilizes dopamine response under stimulatory conditions.
• Balances excitatory/inhibitory signaling through modulation of monoamine turnover.
• Supports adaptive neurochemical responses to environmental and psychological stressors.
• Enhances reward-related signaling pathways, potentially improving motivation and focus.

Immune & Inflammatory Regulation

• Modulates cytokine gene expression and restores Th1/Th2 balance after brain injury.
• Reduces transcription of pro-inflammatory cytokines and chemokines in ischemic tissue.
• Upregulates immune, vascular, and repair-related genes following stroke.
• Supports anti-inflammatory responses while preserving necessary immune activation.

Antioxidant & Anti-Toxic Stress Activity

• Reduces reactive oxygen species (ROS) and free radical accumulation in stressed neural tissue.
• Prevents cognitive damage from lead, molybdenum, and other neurotoxic exposures.
• Protects against oxidative aggregation of amyloid-beta in Alzheimer’s models.
• Chelates transition metals like copper, blocking metal-catalyzed oxidative cascades.

Metabolic & Endocrine Support

• Improves lipid profiles (↓ LDL, TG, cholesterol; ↑ HDL) in diabetic and metabolic models.
• Stabilizes blood glucose under stress and supports insulin-regulatory hormone balance.
• Reduces stress-induced corticosterone surges in animal models of HPA-axis activation.
• Supports cardiometabolic health in research related to stress, diabetes, and atherosclerosis.

Mechanisms of Action

• Stimulates BDNF and TrkB phosphorylation, supporting neuronal growth and plasticity.
• Interacts with melanocortin receptors (MC4/MC5), contributing to anti-inflammatory signaling.
• Inhibits enkephalinase enzymes, prolonging endogenous opioid activity for natural anxiolysis.
• Rapidly alters expression of transcriptional programs involved in stress, inflammation, and repair.

To maximize the utility of Semax in experimental models, researchers often combine it with compounds that enhance its neurotrophic, neuromodulatory, antioxidant, and immunoregulatory effects. These combinations are commonly explored in studies of stroke recovery, cognitive performance, mood regulation, oxidative stress, and neurodegeneration.

Semax Synergistic Compounds

Potential Research Use Cases for Semax Combinations

• Neuroregeneration & Stroke Recovery:
  Semax + Cerebrolysin + BPC-157 + Thymosin Beta-4
  → Supports neuronal plasticity, synaptic remodeling, and vascular regeneration post-ischemia.
• Cognitive Enhancement & Memory Performance:
  Semax + Selank + GHK-Cu
  → Enhances hippocampal learning circuits, focus, and cognitive resilience under stress.
• Neuroprotection & Oxidative Stress Models:
  Semax + GHK-Cu + BPC-157 + Thymosin Beta-4
  → Strengthens antioxidant defense, prevents mitochondrial decline, and aids post-injury neuronal recovery.
• Mood Regulation & Stress Resilience:
  Semax + Selank + Thymosin Alpha-1
  → Synergistic modulation of neurotransmitters, improving mood stability and anxiety control.
  
• Anti-Inflammatory CNS Research:
  Semax + Thymosin Alpha-1 + LL-37 + BPC-157
  → Regulates neuroimmune transcription factors and suppresses pro-inflammatory signaling within the CNS.

Cognitive Enhancement

Semax exhibits pronounced nootropic activity across preclinical and limited human studies. In rats, a single intranasal dose significantly increased hippocampal BDNF and TrkB expression while enhancing conditioned-avoidance learning (Ref. 1). Region-specific regulation of NGF / BDNF mRNA across the cortex, hippocampus, and retina indicates adaptive, area-dependent modulation of plasticity genes (Ref. 12). In vitro, Semax supports cholinergic neuron survival and elevates choline acetyltransferase activity—mechanisms directly linked to learning and memory processes (Ref. 15).

Anxiety, Mood, & Stress Regulation

Chronic Semax administration reduces anxiety- and depression-like behavior in rodent models of chronic unpredictable stress. These effects align with increased serotonergic tone and BDNF up-regulation in limbic structures, supporting an antidepressant-like and anti-stress profile (Ref. 14).

Neuroprotection in Ischemia / Stroke & Functional Recovery

Semax is clinically used in Russia as a neuroprotective and neurorehabilitation agent following ischemic stroke. In a controlled study of 110 patients, intranasal Semax (6 mg / day) elevated plasma BDNF and accelerated motor and functional recovery (Ref. 2). Earlier clinical investigations also reported improved neurological scores in acute hemispheric stroke (Refs. 10–11).
In rodent models of focal and transient middle cerebral artery occlusion, Semax reduced infarct size, preserved spatial learning, and normalized ischemia-disrupted transcriptional programs by suppressing inflammatory and apoptosis-related genes while re-activating neurotransmission pathways (Refs. 3–4). Proteomic studies further confirm activation of protective, anti-oxidative, and synaptic-repair cascades during ischemia–reperfusion (Ref. 16).
Notably, intranasal delivery provides rapid central availability, as demonstrated in radiotracer studies detecting Semax distribution to brain tissues within minutes of administration (formerly described in Ref. 9 but integrated here).

Vision / Optic Nerve Neuroprotection

Semax has been incorporated into ophthalmologic research for optic-nerve and retinal protection. Clinical studies report improved visual acuity, field sensitivity, and optic-nerve electrophysiology in patients with optic neuritis or glaucomatous neuropathy (Refs. 7–8). Intranasal dosing allows ocular and CNS penetration, supporting its observed visual-system efficacy through shared neurotrophic and anti-inflammatory pathways.

Neurotransmitter & Receptor Systems

Semax modulates central monoamines: it increases serotonin levels and potentiates dopaminergic responses to stimulants such as d-amphetamine without substantially altering basal dopamine, demonstrating a stimulus-dependent modulatory effect (Ref. 5). Its structural relation to the ACTH(4-10) fragment enables melanocortin-receptor interactions (particularly MC₄ / MC₅), pathways implicated in stress, appetite, inflammation, and neuroprotection (Refs. 4, 13).

Immune, Inflammatory, & Vascular Gene Regulation

Genome-wide transcriptomics show Semax orchestrates large-scale immune and vascular gene responses after ischemia—over 50 % of modulated genes relate to cytokine signaling, endothelial migration, and tissue repair (Ref. 3). Semax suppresses pro-inflammatory cytokine expression while restoring neurotransmitter-system gene profiles, suggesting combined anti-inflammatory and neurorestorative action (Ref. 4).

Oxidative Stress, Metals, & Amyloid-β Interactions

Semax counteracts oxidative injury and metal-induced toxicity. In heavy-metal-exposed rats, it prevented learning deficits and oxidative damage, demonstrating antioxidant efficacy comparable to ascorbic acid (Ref. 6). In biochemical and cellular models, Semax chelates Cu²⁺ ions, blocking copper-driven Aβ aggregation and protecting neuronal membranes—mechanisms relevant to neurodegenerative research (Ref. 17).

Metabolic Effects (Lipid & Glucose Regulation)

In streptozotocin-induced diabetic rats, Semax (200 µg/kg) improved dyslipidemia—reducing total cholesterol, triglycerides, and LDL while increasing HDL (Ref. 18). These findings highlight favorable modulation of lipid metabolism and stress-hormone homeostasis under metabolic-syndrome conditions.

Enkephalinase / Peptidase Inhibition

Semax inhibits human-serum enkephalin-degrading enzymes in vitro (Ref. 19). By prolonging endogenous enkephalin activity, it may enhance natural analgesic and anxiolytic signaling, contributing to its behavioral and mood effects observed in preclinical studies.