Semax: An ACTH(4-7) Analogue in Neuroprotection and Cognitive Research

Overview

Semax (CAS 80714-61-0) is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, corresponding to the ACTH(4-7) fragment extended with a Pro-Gly-Pro C-terminal sequence that confers resistance to enzymatic degradation. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and has been approved for clinical use in Russia for stroke, transient ischemic attacks, and cognitive disorders.

With a molecular weight of approximately 813 Da, Semax is significantly more stable than the native ACTH(4-7) fragment due to its C-terminal modification. It does not interact with adrenocortical receptors and does not stimulate cortisol production, distinguishing it from full-length ACTH and making it suitable for research applications where HPA axis effects are not desired.

Mechanism of Action

Semax's primary mechanism involves stimulation of brain-derived neurotrophic factor (BDNF) synthesis and release in the hippocampus and other brain regions. BDNF is a critical neurotrophin that supports neuronal survival, synaptic plasticity, and the formation of new memories. Research has shown that Semax increases BDNF mRNA expression and protein levels in the hippocampus, with effects on downstream TrkB receptor signaling that promote neuronal survival and synaptic strengthening.

Semax also modulates the dopaminergic and serotonergic systems. Research has demonstrated that Semax increases dopamine and serotonin turnover in the striatum and frontal cortex, with potential relevance to mood regulation and cognitive function. The peptide has been shown to reduce oxidative stress in neural tissue and to have anti-inflammatory effects in models of neurological injury.

In models of cerebral ischemia, Semax reduces the expression of pro-inflammatory genes and upregulates neuroprotective pathways, including genes involved in VEGF signaling and neurotrophin support.

Key Research Findings

Research in animal models has consistently demonstrated that Semax improves performance in learning and memory tasks, including the Morris water maze and passive avoidance paradigms. These effects have been attributed to BDNF-mediated enhancement of hippocampal synaptic plasticity and neurogenesis.

Clinical research in Russia has examined Semax in stroke rehabilitation, with studies reporting improvements in neurological outcomes and cognitive recovery compared to standard care. A study by Miasoedov et al. demonstrated that intranasal Semax administration improved attention, memory, and executive function in patients recovering from ischemic stroke.

Research has also explored Semax's anxiolytic properties, with animal studies demonstrating reduced anxiety-like behavior in elevated plus maze and open field tests. These effects appear to be mediated through serotonergic mechanisms distinct from benzodiazepine receptor pathways.

Chemical Properties

| Property | Value | |---|---| | Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | | Molecular Weight | ~813 Da | | CAS Number | 80714-61-0 | | Parent Compound | ACTH(4-7) | | Form | Lyophilized powder | | Purity (research grade) | ≥99% HPLC | | Storage | −20°C, protect from light |

Research Considerations

Semax is supplied as a lyophilized powder for research use and is typically administered intranasally in clinical research due to its ability to cross the blood-brain barrier via the olfactory route. Research protocols should account for the route of administration when designing studies, as intranasal delivery produces different pharmacokinetic profiles compared to subcutaneous or intravenous administration. The peptide's BDNF-stimulating mechanism makes it relevant to research in neuroplasticity, cognitive aging, and neurological injury models.

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