Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Semax | SS-31 (Elamipretide) | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril). | Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC. |
| Timing | Morning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery. | Morning dosing preferred. No food timing restrictions. |
| Cycle Duration | 10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns. | Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established. |
| Evidence Level | moderate_human | Emerging (Phase 2/3 trials) |
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of the ACTH(4-10) fragment that rapidly upregulates brain-derived neurotrophic factor (BDNF) and its signaling receptor TrkB in the hippocampus (1.4-fold BDNF protein increase, 3-fold exon III BDNF mRNA increase). It activates dopaminergic and serotonergic brain systems, enhances neurotrophin gene expression (BDNF, NGF), and modulates intracellular calcium dynamics in brain neurons. Semax lacks ACTH's corticotropic activity, acting purely as a nootropic/neuroprotective agent.
Research indicates 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril).
Morning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery.
10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns.
SS-31 (D-Arg-Dmt-Lys-Phe-NH2, also known as elamipretide/Bendavia) is a cell-permeable tetrapeptide that localizes to the inner mitochondrial membrane and binds cardiolipin via electrostatic interactions. This stabilizes cardiolipin against oxidative damage, preserving cristae integrity, reducing ROS production, and maintaining mitochondrial ATP production. SS-31 interacts with proteins in two functional groups: oxidative phosphorylation complexes and 2-oxoglutarate metabolic enzymes — all known cardiolipin binders. It restores mitochondrial function without acting as a direct antioxidant.
Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.
Morning dosing preferred. No food timing restrictions.
Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.
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