PE-22-28 Dosage

PE-22-28 is a synthetic peptide composed of 22 to 28 amino acids and is a derivative of the natural peptide Spadin. This natural molecule is secreted from Sortilin, which exhibits effects that favor neurogenesis, making it potentially effective in treating various depressive states. This neurogenic regulator can lead to resistance to depression, influence neuronal growth, and strengthen the synapses between neurons or their connections with other cells.

The peptide binds to TREK-1 receptors, which are primarily localized in the central nervous system and are involved in processes such as memory and mood regulation. PE-22-28 is more stable in tissues and is considered to have a greater antidepressant potential than Spadin itself. It is believed that this peptide can exhibit properties such as accelerated learning and memory development, which are crucial in the therapy of diseases that have cognitive dysfunction as one of their main symptoms. TREK-1 may also be associated with the balance between muscle contraction and relaxation, which could have clinical applications in the future.

Dosage Chart

About the Peptide

PE-22-28 is a synthetic peptide composed of 22 to 28 amino acids. It is a derivative of the natural peptide Spadin, which is synthesized from the Sortilin. The primary function of this peptide is based on neuroprotective properties and induced neuronal growth. It acts as a neurogenic regulator favoring neurogenesis. This property is crucial because neurons are a type of cell that cannot regenerate themselves but must be produced anew, a complex process that requires the assistance of supplements. PE-22-28 is significantly more stable in tissues and is believed to exert its effects more potently than the original molecule. The peptide binds to TREK-1 receptors, primarily localized in the central nervous system.

Based on all the functions that PE-22-28 performs on the nervous tissue, the assumption is made that the peptide can be effective in treating various types of depressive conditions. The results of studies have confirmed this assumption. Patients have generally reported an improvement in their condition shortly after receiving the peptide. The mechanisms of action are varied but primarily based on neurogenesis. Although depression as a psychosomatic condition can occur for various reasons, the feeling that predominates is sadness.

Due to stressful situations, excessive worry, or other reasons, there is a decrease in the number of neurons and atrophy of the hippocampus (the part of the central nervous system responsible for perceiving feelings). Since neurons do not regenerate spontaneously, PE-22-28 induces biochemical pathways that favor neurogenesis. Additionally, it can affect physical pathways, increasing the volume of the hippocampus, which consequently improves the condition. Similar effects are also produced by classic SSRI antidepressants, which are used as the most common therapy. Still, due to side effects such as decreased cognition and decreased libido, it is believed that this peptide can replace them.

After the discovery of the potent antidepressant effect of this peptide, it was assumed that the same effect could be achieved in cases of secondary depression when the disease develops as a complication. In patients diagnosed with a stroke, a primary condition occurs characterized by poor blood flow to the brain. In the case of survival, serious psychophysical consequences are possible, including depression. By enhancing neurogenesis and stimulating the growth of existing neurons, PE-22-28 has antidepressant potential and improves mood. Most patients included in studies who developed depression after stroke reported stabilization of mood, absence of suicidal thoughts, and improvement in quality of life. The effects above may also be beneficial in cases of Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions where depression may also occur in a secondary form.

Another beneficial effect of this peptide may be its effect on muscle function. It is assumed that the level of expression of TREK-1 receptors plays an essential role in the response of muscles to stimuli. Increased expression may contribute to muscle relaxation, while reduced expression of these receptors may favor contraction. Although this effect has not been thoroughly studied, it is believed to be crucial in treating conditions where functional muscle is essential, such as bladder myogenic dysfunction or various forms of myogenic diseases.

List of Uses

Antidepressant Effect

Depression is a psychiatric condition characterized by a pronounced feeling of sadness and negativity. Patients often experience a lack of motivation, nothing brings happiness, and they see no point in continuing their lives. If left untreated, depression can lead to suicidal thoughts and death. The most common therapy used so far has been antidepressants from the SSRI (Selective Serotonin Reuptake Inhibitors) group, which have shown relatively good results. However, they have exhibited many side effects, such as loss of libido, sleepiness, amnesia, or even an opposite effect, which further exacerbates depression. In addition, they usually take a long time to react and provide the first improvement in patients (a few months). PE-22-28 has a much faster onset of action (a few days), is more potent, and does not cause serious side effects. Due to these properties, it is believed that the peptide may eventually replace SSRI antidepressants.

The mechanisms of action are diverse but are mainly based on the action of the peptide on various parts of the central nervous system that are responsible for the perception of emotions. According to scientific studies, the hippocampus in these patients is atrophic (reduced). At the same time, after the application, its volume increases (which is achieved by acting on various biochemical pathways). In addition, the peptide acts by inducing neurogenesis (the process of creating new neurons). This work is crucial because a significantly lower number of neurons has been observed in depressed patients than in psychologically healthy patients. PE-22-28 can also stimulate the growth of neurons, thereby improving the health of the remaining cells.

Improved Post – Stroke Recovery

A stroke is an acute neurological condition that occurs due to compromised circulation resulting from reduced blood flow to the brain and leading to ischemia of brain tissue. This condition is often fatal, and in the case of survival, various psychological and physical consequences are possible, including depression. Since it usually occurs suddenly, patients have a hard time coping with consequences such as paralysis, disorientation, or difficulty moving. In this case, depression occurs as a secondary condition but has the same symptoms as the primary one.

Using similar mechanisms of action, such as stimulation of neurogenesis, induction of neuronal growth, or an increase in hippocampal volume, depressive episodes in these patients may last shorter, be less intense, and their frequency may significantly reduce. In addition, cognitive dysfunctions in the form of impaired reasoning, learning, and memory may occur after a stroke. Scientists believe that PE-22-28 may help improve cognition and stabilize mood, thereby enabling patients to restore functionality and meaning in their lives.

These properties may also be helpful in other conditions where cognitive errors occur as a consequence of the pathogenesis of the disease in addition to depression itself. Such a case may be neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease.

Impact on Muscle Function

Although this property has not been thoroughly studied, it is believed that PE-22-28 may affect muscle contraction. This assumption is based on the fact that the level of TREK-1 receptor expression correlates with muscle activity. A large number of receptors and the subsequent binding of the peptide can result in muscle relaxation. On the other hand, low receptor expression leads to a greater chance of muscle contraction. This property may be used to treat diseases where there is a balance disorder in the direction of contraction or excessive relaxation.

Dosage Calculator

This peptide is most often used to treat primary and secondary depressive states. The optimal dose is 400 mcg, administered as a nasal spray at the beginning of treatment. The dose is administered once daily, most often in the morning. However, some opinions suggest that this dose is too small and that it should be 400 mcg for each nostril. Later, the maintenance dose can be increased to a maximum of 600mcg, and the method of administration remains the same. The solution is typically prepared independently, according to the manufacturer's instructions.

Conclusion

PE-22-28 is a derivative of the natural peptide Spadin. According to scientific studies, it exhibits numerous beneficial effects, with some of the most important being its potential role in treating primary and secondary depressive states, enhancing recovery after stroke, and its potential impact on muscle contraction. The peptide must be used at an optimal dose, which should not be changed or discontinued independently. Indications limit its use, and the maximum dose should not be exceeded. Regardless of the achievements made so far, PE-22-28 will continue to be a subject of research.

References:

1. Okada, Masayoshi, and Ernesto Ortiz. "Viral vector-mediated expressions of venom peptides as novel gene therapy for anxiety and depression." Medical Hypotheses 166 (2022): 110910.
2. Mental health: spadin, a fast-acting antidepressant. https://journals.biologists.com/dmm/article/3/7-8/398/2435/Mental-health-spadin-a-fast-acting-antidepressant
3. Djillani, A., Mazella, J., Heurteaux, C., & Borsotto, M. (2019). Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Frontiers in pharmacology, 10, 379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470294/
4. Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017 Sep 12;8:643. https://pubmed.ncbi.nlm.nih.gov/28955242/
5. Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M, Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G, Nahon JL, Heurteaux C, Borsotto M. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010 Apr 13;8(4):e1000355. https://pubmed.ncbi.nlm.nih.gov/20405001/