DihexavsN-Acetyl Semax Amidate

Molecular Formula

C₂₇H₄₄N₄O₅

Molecular Weight

504.7 g/mol

Half-Life

~12 days (following IV administration in rats)

Bioavailability

Orally active and blood-brain barrier permeable — specific oral bioavailability percentage not published

CAS Number

1401708-83-5

Molecular Formula

C₃₉H₅₄N₁₀O₁₀S

Molecular Weight

855.0 g/mol

Half-Life

Extended compared to native Semax; parent Semax has a plasma half-life of minutes, but pharmacological effects persist for hours due to intracellular signaling cascade initiation. N-Acetyl Semax Amidate achieves significantly longer effective duration

Bioavailability

Enhanced intranasal and subcutaneous bioavailability compared to native Semax; dual terminal modifications prevent enzymatic degradation from both ends

CAS Number

Not assigned (N-Acetyl Semax Amidate); 80714-61-0 (parent Semax)

Common

• Headache
• Vivid dreams or altered sleep patterns
• Emotional sensitivity
• Mild fatigue during adjustment

Uncommon

• Gastrointestinal discomfort

Serious

• Theoretical oncogenic risk from c-Met activation

Common

• Nasal irritation
• Headache
• Mental overstimulation or restlessness
• Sleep difficulty
• Appetite changes

Uncommon

• Hair darkening

Serious

• Allergic reaction

Evidence Level

Preclinical only — animal and cell-culture studies; no human trials

FDA Status

Research compound

Safety Overview

Dihexa has demonstrated a favorable safety profile in published animal studies, with no reported tumorigenic effects or organ toxicity at cognitive-enhancing doses. However, the compound has not undergone formal human clinical trials, and long-term safety data does not exist. The primary theoretical safety concern is sustained activation of the HGF/c-Met proto-oncogenic pathway, which could theoretically promote tumor initiation or growth. The extremely long half-life (~12 days) raises additional concerns about compound accumulation with chronic daily dosing. Anecdotal reports from the nootropics community generally describe good tolerability at doses of 5-20 mg daily, with headaches and vivid dreams as the most commonly reported effects.

Contraindications

• xKnown or suspected malignancy — c-Met/HGF pathway activation may promote tumor growth
• xPregnancy and breastfeeding — no safety data available
• xHistory of cancer, particularly HGF/c-Met-driven tumors (hepatocellular, gastric, lung)
• xSevere hepatic impairment

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

N-Acetyl Semax Amidate shows excellent safety tolerability in Russian clinical studies with no serious adverse events reported at therapeutic doses. The amidate modification significantly enhances CNS penetration and metabolic stability compared to parent Semax, reducing dosing frequency. Side effects are primarily mild nasal irritation, transient headaches during initiation, and rare increases in dopaminergic tone manifesting as restlessness or insomnia at high doses, easily managed through dose adjustment.

Contraindications

• xKnown hypersensitivity to Semax, ACTH fragments, or any formulation component
• xPregnancy and breastfeeding — insufficient safety data in these populations
• xActive seizure disorders — neurostimulatory effects may lower seizure threshold in susceptible individuals
• xAcute psychotic episodes — dopaminergic and neurostimulatory effects may exacerbate symptoms