Semax vs Noopept: Comparing Cognitive Enhancing Peptides

Semax vs Noopept | What to Know in 2024

Semax and Noopept are both nootropics under investigation for their abilities to enhance learning, improve memory, protect the brain from injury, and reduce anxiety. Both peptides are derivatives of natural compounds and have been extensively studied in animal models to determine safety and efficacy. Despite the research into the properties of Semax and Noopept, a great deal remains to be learned about the actions of these peptides in the central nervous system. The most extensive work for both peptides has been to investigate their abilities to mitigate the effects of stroke, but work has also been done on their abilities to enhance cognitive function in healthy individuals. Both peptides have been around for decades, but Semax has garnered more attention, particularly in Russia.

Semax vs Noopept

Noopept has been investigated for its ability to reduce the neurotoxic effects of excess calcium following brain injury. In vitro and in vivo research have both revealed that Noopept decreases the extent of necrotic damage caused by brain ischemia[1]. Semax has also been investigated as a potential treatment for stroke, but it operates in two different ways. First, Semax appears to regulate the expression of nearly 40 different genes in the setting of brain injury. This leads to increases interferon signaling and helps to decrease the natural stress response. Second, Semax reduces clotting by reducing platelet activation. This reduces the hypercoagulable state found in certain types of stroke[2].

Semax appears to work primarily by altering gene expression patterns in the brain while Noopept is thought to work via as-yet-unknown receptor interactions. While the two peptides have very different mechanisms of action, their effects are similar in many ways. This suggests that they both ultimately influence one or more common pathways in the central nervous system responsible for neuroprotection, stress responses, and neuron growth.

Perhaps the biggest difference between Semax and Noopept is their routes of administration. While both peptides can be administered parenterally (e.g., IV or SubQ), only Noopept can be taken by mouth. Its small size, high potency, and relative resistance to the environment of the GI tract make Noopept and effective oral research nootropic. The peptide is currently being investigated in both 5 mg and 10 mg oral preparations to determine its efficacy and safety[3]. Semax can be administered via nasal spray, another form of parenteral administration that may make the peptide as simple to utilize as Noopept.

Research into Semax is more extensive. The result is that more is known about the functions of Semax outside of the central nervous system. Semax has been shown, in rat models, to affect nervous system growth in the peripheral nervous system and thus has been shown to have effects on tissues in the cardiovascular system. Research shows that Semax can lower blood pressure and may be effective in mitigating the effects of heart attack[4], [5].

What Is Semax?

Semax is a short, synthetic peptide derived from adrenocorticotropic hormone (ACTH). Research shows that Semax plays important roles in the regulation of gene expression in the central nervous system both during health and during injury.

In rat models of brain injury, Semax has been shown to increase cytokine levels, reduce stress responses, and enhance the effects of interferon signaling to modulate the immune response. Following stroke, Semax has been shown to greatly increase brain-derived neurotrophic factor (BDNF) following ischemia. This results in improvements in rehabilitation following stroke.

It is the ability of Semax to boost BDNF levels that also accounts for much of the peptide’s nootropic abilities. Research in healthy rats shows that Semax can increase BDNF , particularly in the forebrain, to improve learning and memory formation[6]. Research suggests that Semax activates the default mode network in the brain. The default mode network is an interconnected system of brain regions that is important in memory, executive function, and our ability to recognize and think about “self[7].”

Semax Structure

Sequence: Met-Glu-His-Phe-Pro-Gly-Pro

Molecular Formula: C₃₇H₅₁N₉O₁₀S

Molecular Weight: 813.928 g/mol

PubChem CID: 122178

CAS Number: 80714-61-0

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What Is Noopept?

Noopept is a short peptide consisting of just two amino acids. This dipeptide (Pro-Gly) is a derivative of Piracetam, a long-studied nootropic agent shown to improve memory, attention, and learning in certain settings. Piracetam is an anti-convulsant and itself a derivative of the neurotransmitter gamma-aminobutyric acid (GABA).

Noopept is 20,000 times more active than piracetam, however, because of its much smaller size and thus ability to more effectively penetrate the blood-brain barrier (BBB). Noopept, at just two amino acids in length, is effective at doses 1000 times lower than piracetam[8], [9].

Noopept has been shown, in animal studies, to have three key activities in the central nervous system. It is

• Nootropic – reducing memory deficits following injury and increasing the ability of the brain to form and consolidate memories,

• Neuroprotective – ameliorating the behavioral and cognitive consequences of Alzheimer’s disease and stroke in multiple animal models, and

• Anxiolytic – reduces anxiety as a result of its GABA-like effects[8].

Noopept Structure

Sequence: benzylcarbonyl-Pro-Gly-OEt (PG)

Molecular Formula: C₁₇H₂₂N₂O₄

Molecular Weight: 318.4 g/mol

PubChem CID: 180496

CAS Number: 157115-85-0

Pseudonyms: Oberacetam, SGS-111, Pyroglutamyl

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Semax vs Noopept: A Structural Comparison

A look at the structural differences between Semax and Noopept reveals an obvious difference. While both are small peptides, Noopept is significantly smaller at just two amino acids versus seven. While this may seem like a trivial difference, dipeptides like Noopept are much more likely to cross the blood-brain barrier. This is one reason that Noopept is effective as an oral agent and is why Noopept can be useful at much, much lower dosages than Semax.

The other difference of note between these two peptides is the benzylcarbonyl group that is added to Noopept. This modification makes Noopept more resistant to certain chemical environments and is, in part, why the peptide can survive the conditions of the GI tract. A benzylcarbonyl could be added to Semax, but it might impact the peptide’s absorption properties. As a dipeptide, Noopept can afford the addition without any great sacrifice to its potency.

Semax vs Noopept: Summary

Semax and Noopept share a great deal in common even if their structures and mechanisms of action are different. The two peptides are also different in many ways, not the least of which is their routes of administration. Further research on both peptides will help to elucidate the mechanisms by which the brain functions and protects itself. Perhaps most interesting, however, is the yet unanswered question about whether these two peptides might work synergistically to produce even greater neuroprotective and nootropic effects. Animal studies looking at potential co-administration regimes remain to be done but hold a great deal of promise in for brain health.