Semax: A Comprehensive Guide to the ACTH(4-7) Heptapeptide
An in-depth examination of Semax (Met-Glu-His-Phe-Pro-Gly-Pro), its mechanism of action involving BDNF/NGF upregulation, melanocortin receptor binding, and its neuroprotective properties in preclinical research.
Introduction
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the adrenocorticotropic hormone (ACTH) sequence. Developed in Russia during the 1980s, it has been extensively studied for its nootropic and neuroprotective properties. This guide provides a comprehensive overview of Semax from a research perspective.
Chemical Structure
Semax corresponds to ACTH(4-7) extended with a Pro-Gly-Pro tripeptide. This C-terminal extension confers resistance to enzymatic degradation, extending the half-life significantly compared to the native ACTH fragment.
- Molecular Formula: C37H51N9O10S
- Molecular Weight: ~813.9 g/mol
- Appearance: White to off-white lyophilized powder
- CAS Number: 80714-61-0
Mechanism of Action
Semax operates through multiple pathways:
1. BDNF and NGF Upregulation
Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are critical proteins for neuronal survival, synaptic plasticity, and learning. Preclinical studies demonstrate that Semax upregulates BDNF expression by approximately 5-fold in the hippocampus and cortex.
2. Melanocortin Receptor Binding
Semax binds to melanocortin receptors (particularly MC4R) with moderate affinity. This interaction modulates cognitive processes, including attention and memory consolidation.
3. POMC-Derived Peptide Modulation
Semax influences the degradation rate of proopiomelanocortin (POMC)-derived peptides, indirectly affecting enkephalin levels and endogenous opioid activity.
4. Neuroprotective Effects
In models of transient focal cerebral ischemia, Semax reduces infarct volume by up to 30% when administered within the therapeutic window. The mechanism involves:
- Reduction of oxidative stress markers
- Preservation of mitochondrial function
- Modulation of inflammatory cytokine cascades
Preclinical Research Findings
Cognitive Enhancement
In shuttle-box avoidance paradigms, Semax-treated animals demonstrated:
- 40% improvement in active avoidance acquisition
- Enhanced consolidation of spatial memory in Morris water maze
- Attentional improvements in serial reaction time tasks
Neuroprotection
Studies in ischaemic and hypoxic models consistently show:
- Reduced neuronal death in CA1 hippocampal regions
- Preservation of blood-brain barrier integrity
- Attenuation of glial activation markers
Stress Response Modulation
Semax does not produce the steroidogenic effects typical of full-length ACTH. It modulates the HPA axis without significantly elevating corticosterone levels.
Analytical Characterisation
All research-grade Semax should meet the following specifications:
| Parameter | Specification |
|---|---|
| Purity | >= 98% (HPLC) |
| Identity | Confirmed by mass spectrometry |
| Residual solvents | < ICH Q3C limits |
| Bacterial endotoxins | < 10 EU/mg |
| Appearance | White to off-white lyophilized powder |
Storage and Handling
- Store at -20C in a dry environment
- Protect from direct sunlight
- Reconstitute with bacteriostatic water for research applications
- Use within 30 days of reconstitution when stored at 2-8C
Frequently Asked Questions
What is the molecular weight of Semax?
Semax has a molecular weight of approximately 813.9 g/mol.
Is Semax the same as ACTH?
No. Semax is a 7-amino-acid fragment of ACTH (positions 4-7) extended with Pro-Gly-Pro. It lacks the steroidogenic effects of full-length ACTH.
What is the CAS number for Semax?
The CAS number for Semax is 80714-61-0.
Conclusion
Semax represents a fascinating tool for neuroscience research, with well-characterised effects on neurotrophin expression, melanocortin signalling, and neuroprotection. All products sold by Kingston Peptides are intended exclusively for in vitro research and analytical purposes.