Peptide Comparison
N-Acetyl Semax AmidatevsDihexa
Doubly modified ACTH(4-7) analogue heptapeptide with potent nootropic, neuroprotective, and neurotrophic properties acting through BDNF/NGF upregulation and transcriptome-level modulation of inflammatory and neurotransmitter gene networks
Angiotensin IV-derived oligopeptide that potentiates hepatocyte growth factor to drive synaptogenesis and cognitive enhancement with extraordinary potency
At a Glance
Quick
comparison
Dose Range
N-Acetyl Semax Amidate
0.1–0.6 mg
Dihexa
5–20 mg
Frequency
N-Acetyl Semax Amidate
Once daily
Dihexa
Once daily
Administration
N-Acetyl Semax Amidate
Intranasal spray
Dihexa
Oral (capsule/tablet)
Cycle Length
N-Acetyl Semax Amidate
8-12 weeks
Dihexa
4-6 weeks
Onset Speed
N-Acetyl Semax Amidate
Rapid (hours to days)
Dihexa
Moderate (1-2 weeks)
Evidence Level
N-Acetyl Semax Amidate
Moderate human trials (Phase 1-2)
Dihexa
Strong human trials (Phase 3 or FDA approved)
Efficacy
Benefit
ratings
Recovery
Growth
Cognitive
Healing & Recovery
Anti-Aging
Technical Data
Compound
specifications
N-Acetyl Semax Amidate
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)
Dihexa
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
Protocols
Dosing
tiers
N-Acetyl Semax Amidate
Dihexa
Applications
Best
suited for
N-Acetyl Semax Amidate
Cognitive enhancement through BDNF and NGF-mediated neuroplasticity
N-Acetyl Semax Amidate is particularly well-suited for individuals focused on cognitive enhancement through bdnf and ngf-mediated neuroplasticity. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Neuroprotection during and after cerebral ischemic events or brain injury
N-Acetyl Semax Amidate is particularly well-suited for individuals focused on neuroprotection during and after cerebral ischemic events or brain injury. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Nootropic stacking for enhanced learning, memory, and cognitive processing speed
N-Acetyl Semax Amidate is particularly well-suited for individuals focused on nootropic stacking for enhanced learning, memory, and cognitive processing speed. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Attention and focus improvement for cognitively demanding tasks
N-Acetyl Semax Amidate is particularly well-suited for individuals focused on attention and focus improvement for cognitively demanding tasks. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Dihexa
Age-Related Cognitive Decline
Dihexa directly addresses the synaptic loss that underlies age-related cognitive decline by building new functional synaptic connections in the hippocampus. Animal studies demonstrate restored spatial learning in aged rats, making it a compelling candidate for combating memory loss associated with aging.
Neuroplasticity Enhancement
Unlike nootropics that work through neurotransmitter modulation, dihexa drives physical neuroplasticity — the formation of new dendritic spines and synapses. This makes it ideal for individuals looking to enhance their brain's capacity for learning and adaptation at a structural level.
Neurodegenerative Disease Research
Preclinical evidence in APP/PS1 Alzheimer's mice and scopolamine-induced amnesia models positions dihexa as a leading research compound for neurodegenerative disease. It is patented for potential use in Alzheimer's and Parkinson's diseases, with ongoing interest from the research community.
Advanced Nootropic Stacking
Dihexa's unique mechanism (HGF/c-Met potentiation) is complementary to most other nootropic mechanisms, making it an excellent addition to advanced cognitive enhancement protocols when combined with choline donors, racetams, or adaptogens.
Safety Profile
Side
effects
N-Acetyl Semax Amidate
Common
- Nasal irritation
- Headache
- Mental overstimulation or restlessness
- Sleep difficulty
- Appetite changes
Uncommon
- Hair darkening
Serious
- Allergic reaction
Dihexa
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
Research Status
Safety
& evidence
N-Acetyl Semax Amidate
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
Dihexa
Evidence Level
Strong human trials (Phase 3 or FDA approved)
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
Decision Guide
Which is
right for you?
Choose N-Acetyl Semax Amidate if...
- Cognitive enhancement through BDNF and NGF-mediated neuroplasticity
- Neuroprotection during and after cerebral ischemic events or brain injury
- Nootropic stacking for enhanced learning, memory, and cognitive processing speed
- Attention and focus improvement for cognitively demanding tasks
Choose Dihexa if...
- Cognitive enhancement and memory consolidation in age-related decline
- Supporting neuroplasticity and new synaptic connection formation
- Research into neurodegenerative disease therapeutics (Alzheimer's, Parkinson's)
- Nootropic stacking for individuals seeking enhanced learning capacity