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AOD9604 5mg/10mg
Hunger and satiety signals are controlled by serotonin, dopamine, norepinephrine and a number of other systems within our body. When talking about weight loss and appetite modulation, there are agents that do it through pure central nervous system pathways, and those that target peripheral signals (that travel to the central nervous system).
This is why we have so many different weight loss options, since medication is based on substances affecting different pathways, signals and weight management systems. One such drug, aimed at improving adipose tissue function and fatty acid metabolism is AOD9604.
AOD9604 is a modified form of human growth hormone fragment 176-191, developed to stimulate prolipid mobilizing and lipid oxidation (during which fatty acids decompose into carbonyl compounds, unsaturated aldehydes, ketones and other substances).
Even though AOD9604 has not yet been deemed FDA-approved,a number of studies showed its administration led to a significant weight loss and improvements in glucose tolerance (in both animal and early stage human studies).
Another such study done on 300 obese individuals in Australia showed that AOD9064 administration more than tripled weight loss in test subjects, compared to those on a placebo drug. Furthermore, this study proved that long-term treatment is not likely to cause resistance to AOD9064 based medication, making it a perfect candidate for future weight loss medication and treatment.
So far, animal and human studies both showed AOD9064’s effectiveness in helping test subjects lose weight, improve glucose tolerance, while presenting with minimal side effects. Further research studies are needed before including it into an FDA-approved treatment procedure, but the initial findings show a great potential.
Reference:
Michael D. Jensen. Potential Role of New Therapies in Modifying Cardiovascular Risk in Overweight Patients with Metabolic Risk Factors. 06 September 2012
$50.00 – $90.00
| Quantity: | 5mg, 10mg |
|---|---|
| Unit: | 1 vial |
| Contents: | AOD9604 |
| Form/Appearance: | Lyophilized/Powder |
| Peptide Purity: | 99% |
| Sequence: | Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe Disulfide bridge Cys7-Cys14 |
| Molecular Mass: | 1815.12 g/mol |
| Solubility: | Sterile / Bacteriostatic water |
| Synonyms: | AOD 9604 |
FAQs
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Melanotan 2 is a synthetic version of human alpha-melanocyte stimulating hormone and acts as a non selective melanocortin-receptor agonist. It was mainly developed as a sunless tanning option, but some clinical studies showed it also causes spontaneous penile erections, as well as general sexual stimulation.
Some of the other “side effects” researchers noticed were reduction in compulsive behavior, reduced glucagon production, hunger suppression and even some limited addiction control.
Melanotan 2 Effects On Autism
There is some additional recent clinical research suggesting there might be a link between Mealnotan 2 and autism. Of course, melanotan treatment cannot reverse autism, sadly, but it may act on some aspects of this disorder and make it more manageable.
In mouse model studies researchers recorded that MT2 stimulated oxytocin release, which had the potential to reduce (in some cases counteract) common ASD behaviors – behaviors that include:
- Hand clapping
- Bouncing on toes
- Body rocking
- Holding body parts in unusual positions
- Repeating vocalizations etc.
Obesity’s become a global pandemic, currently affecting one third of the entire population, and this is why we can look at it as a chronic disease that requires appropriate treatment.
When talking about obesity, amylin hormone is of great importance as it gets secreted along with insulin and acts as food intake inhibitor, delaying gastric emptying and suppresses post-prandial glucagon responses to meals.
For this reason, there is a tendency to include amylin management in newly developed medication.
And one such compound is cagrilintide – lipidated long-acting amylin analogue.
Though it still hadn’t been thoroughly tested on humans, numerous rat studies showed incredible potential. One such in vitro study involving rats set out to compare cagrilintide’s effectiveness against pramlintide (an FDA-approved diabetes 1/2 medication).
The study showed that pramlintide reduced food intake by 25% in the period of 0-24 hours (it did not cause reduced food intake after 24 hours). But the dosage was substantial – 1000 nmol/kg.
On the other hand, cagrilintide was able to reduce food intake by approximately 50% with a minimal dosage of only 3 nmol/kg. More importantly, this food intake reduction spanned across 60 hours from the moment it was injected.
These results clearly show the potency of cagrilintide in weight loss and diabetes management medication, especially because it acts over such a long time period (allowing subcutaneous injections to be applied once a week).
Reference:
Dehestani B, Stratford NR, le Roux CW. Amylin as a Future Obesity Treatment. J Obes Metab Syndr. 2021 Dec 30;30(4):320-325. doi: 10.7570/jomes21071. PMID: 34929674; PMCID: PMC8735818.
CJC-1295 is a synthetic analogue of growth hormone-releasing hormone (GHRH) and growth hormone secretagogue (GHS) developed by ConjuChem Biotechnologies.
GHRH is a 44-amino acid long peptide which our hypothalamus synthesizes and in the pituitary gland, it binds to the growth hormone (GH) receptors, resulting in the release, regulation and pulsatile secretion of GH.
We already talked about GH therapy as being FDA approved in conditions such as GH deficiency, Turner syndrome, Prader-Willi syndrome, idiopathic short stature etc. Recombinant human GH treatment is generally performed as one daily, subcutaneous injection which elevates the levels of GH serum in the blood.
One of the major problems with this approach to treatment is that the efficacy of GH therapy is hard to determine due to the lack of biological serum biomarkers. Currently, most facilities are using levels of IGF-1 and IGFBP-3 to monitor the efficacy of this therapy but these levels may vary wildly (due to growth velocity, glucose tolerance, insulin levels etc.).
Furthermore, GH abuse extended across multiple sports disciplines, making it even harder to suppress and put this problem under control.
Researchers hope to solve this problem by employing new biomarkers of GH action and secretion. One such way is to employ newly developed molecules, such as CJC-1295, shown to increase both GH and IGF-1 levels in the blood, without affecting the pulsatility of GH secretion. CJC-1295 also has a prolonged half-life of 8 to 10 days, due to its ability to bind to the endogenous serum albumin.
So, what scientists are hoping to achieve with CJC-1295 is both a safe way of promoting GH secretion as well as making it measurable in a laboratory setting. There were numerous studies tackling this issue, but we still need further testing to confirm these preliminary findings.
Reference:
Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res. 2009 Dec;19(6):471-7. doi: 10.1016/j.ghir.2009.03.001. Epub 2009 Apr 21. PMID: 19386527; PMCID: PMC2787983.
If you’re a peptide researcher (or plan on becoming one), you should know the difference between CJC-1295 and CJC-1295 DAC. CJC-1295 DAC features an additional component at the end of the peptide chain, also known as a drug affinity complex or DAC.
This small fragment changes the peptide’s functionality and extends its half-life to six to eight days. It might have a prolonged effect of up to two weeks.
Below, we will showcase the main similarities and differences between these two peptides, including their properties, characteristics, and mechanism of action.
What is CJC-1295 DAC peptide?
This peptide resembles the regular CJC-1925 since it is a modified form of natural GHGR (1-29). However, this one differs from CJC-1925. It has an additional molecule known as a “drug affinity complex.”
DAC features a couple of oxygen and nitrogen atoms connected by chemical bonds. According to some findings, this small number of atoms could significantly impact peptide breakdown rate and its use in the body.
What is CJC-1295 Peptide?
This peptide is also known as “modified growth hormone releasing factor (1-29)”, “ModGRF 1-29”, or “Modified GRF (1-29).” You may also encounter the name “CJC-1295, without DAC.”
All these names imply a specific peptide molecule containing a short amino acid chain. As many studies have indicated, this peptide may boost growth hormones in the bloodstream.
Growth hormone may have a significant role in several vital internal activities. It could facilitate cellular reproduction, repair, and growth, help with tissue repair, improve muscle cell development, support skin cells, and other functions.
While the body naturally produces growth hormone, this production tends to naturally decrease. According to some research done in laboratory settings, CJC-1295 may encourage the natural production of growth hormone, increasing its levels, which could lead to quicker repair, fat cell burn, and muscle cell growth.
Differences between CJC-1295 DAC and CJC-1295
As research studies have outlined, here are some fundamental differences between these two peptides.
Half-life
The main distinction lies in their half-lives. CJC-1295 is thought to mimic the body’s natural peptide. The endogenous GHRH has a short half-life of just a couple of minutes. Similarly, CJC-1295 has a brief half-life of around half an hour.
Regarding the second peptide, the additional DAC could significantly alter the organism’s peptide use. Researchers believe that DAC offers a peptide, a lysine linker, which could protect and prevent it from degrading.
Moreover, the DAC component could extend the half-life of this peptide to about six to eight days.
Properties of CJC-1295 DAC peptide
It is believed that CJC-1295 DAC boosts growth hormone levels in the bloodstream. Additionally, several studies suggest the following:
- Scientists and researchers need to focus their attention to studying the potential of growth hormones on growth and muscle recovery.
- Growth hormone may help convert fatty tissue into energy.
- Growth hormones are linked with collagen production in the skin, which means this peptide may also help with skin regeneration and skin cell development.
- CJC-1295 DAC may positively impact sleep patterns.
- Growth hormone is essential for tissue regeneration and helps the organism recover from damage.
References:
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683.
Sam L. Teichman, Ann Neale, Betty Lawrence, Catherine Gagnon, Jean-Paul Castaigne, Lawrence A. Frohman, Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults, The Journal of Clinical Endocrinology & Metabolism, Volume 91, Issue 3, 1 March 2006, Pages 799–805,
Tesamorelin is a 44 amino acid long, synthetic growth hormone releasing hormone (GHRH) analogue. It was primarily developed and used to treat visceral fat buildup in HIV positive patients suffering from lipodystrophy (a condition characterized by abnormal fat distribution).
Tesamorelin peptide activates GHRH receptors in the pituitary gland, resulting in growth hormone synthesis and release. This GH release further stimulates the production of Ilike growth factor-1 (IGF-1), which is naturally low in obese and diabetic patients.
The good thing about tesamorelin is that it was approved in the US back in 2010 for the treatment of abdominal fat in HIV positive patients as a part of the antiviral therapy-related lipodystrophy. It has also been evaluated as a potential therapy of insulin resistance, nonalcoholic fatty liver and, of course, obesity. These clinical studies are still ongoing and we’ll need more information to confirm its effectiveness.
The usual tesamorelin dosage for patients is 2mg given in the form of a subcutaneous injection, once a week. As for the side effects, patients did not report that many, but from the ones we have documented, most common are:
- Application site irritation
- Itching
- Peripheral edema
- Mild nausea
- Redness
More importantly, tirzepatide therapy was not associated with hepatotoxicity and is very unlikely to cause any clinically apparent liver injuries.
Reference:
Semax is an interesting nootropic that can capture the attention of researchers, health professionals, and enthusiasts alike. It was originally developed in Russia back in the 1980s and 1990s. Nowadays, Semax is believed to enhance a range of cognitive and neuroprotective properties.
Many know this peptide by its trade name, such as Semaxum, and it has been extensively researched by institutions such as the Institute of Molecular Genetics of the Russian Academy of Science.
What is Semax?
Semax is a peptide best known for its neurogenic, neuroprotective, and nootropic properties. It was developed based on the molecular structure of ACTH or adrenocorticotropic hormone. Preliminary studies in small-scale human trials, animals, and cells indicate potential benefits of Semax use.
In the U.S. and multiple countries around the world, this component is the basis for a number of medicines that are used in clinical practices for the treatment of optic nerve atrophy, dys-circulatory encephalopathy, and ischemic brain stroke.
Potential benefits
Some of the benefits Semax may include:
- Increased short-term memory and attention
- Better non-proliferative diabetic neuropathy
- Can assist during recovery from hypoxia/stroke
- Can help with glaucoma optic neuropathy
- May act as an analgesic
- It may help in treating ADHD
- It may help protect the brain from various types of damage and stress
How Does Semax Work?
Semax increases BDNF or brain-derived neurotrophic factor. BDNF is one of the most active neurotrophins, which help control and stimulate neurogenesis, creating new neurons in the brain. This component helps support neuroplasticity, allowing nerve cells in the brain to adapt to new situations and recover from injury.
Additionally, BDNF encourages the survival of existing neurons and supports the growth, creation, and regeneration of new synapses and neurons.
This nootropic also helps minimize the breakdown of enkephalins. Enkephalins are mostly involved in reducing inflammation, decreasing pain, boosting immune cell activity, and preventing cancer cell growth.
They also play a role in pain, emotional behavior, learning, and memory. Balanced enkephalins are necessary to maintain normal brain function. Therefore, researchers are led to believe that Semax may potentially relieve pain. However, more research is needed to confirm the preliminary findings.
References:
Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. 2014 Mar 24;15:228. doi: 10.1186/1471-2164-15-228. PMID: 24661604; PMCID: PMC3987924.
https://www.sciencedirect.com/science/article/abs/pii/S0306987706005391
Gusev, E. & Martinov, Michail & Kostenko, E. & Petrova, Lyudmila & Bobyreva, S.. (2018). The efficacy of semax in the tretament of patients at different stages of ischemic stroke. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 118. 61. 10.17116/jnevro20181183261-68.
Cerebrolysin is a porcine-derived peptide preparation, with a low molecular mass and a variety of research applications. An interesting thing about cerebrolysin is that its preparation contains nerve growth factors, BDFN (brain derived neurotrophic factor), Ciliary nerve growth factor, p-21 and orexin. This means that cerebrolysin contains molecules with:
- Pharmacodynamic properties – it expresses biochemical, physiological and molecular effects within the body.
- Neurotrophic properties – it aids in growing, repair and neuron maintenance
- Neuroprotective properties – it strengthens the neural pathways as well as the neurons themselves and improves synaptic plasticity.
Cerebrolysin Chemical Structure
It’s a bit difficult talking about cerebrolysin as it does not have a single chemical structure, rather, it’s a combination of several different peptides. As such, cerebrolysin is actually labeled an “orphan drug” by the FDA. What this means is it did show promise in disease treatment and prevention (in clinical trials), but only in orphan diseases. Orphan disease is one that affects fewer than 200,000 people in the US. This is why this peptide mix is not a profitable venture for further, independent studies, and research is only possible with financial help from the government.
But in the particular case of cerebrolysin, the government did, in fact, intervene, due to its potential in dealing with dementia and because of its neuroprotective capabilities.
This peptide mix was first developed in Austria, back in 1940 and has since become a vital medicine in Asia, especially Russia and China. Research studies showed that it has the ability to cross the blood-brain barrier and express its pharmacodynamic effects on both brain and the spinal cord.
But, what does it do?
Since cerebrolysin is not a single chemical compound, as we already said, we can look at it, and its effects, through the components its made of:
- Brain-Derived Neurotrophic Factor (BDNF) – this is a protein found in our central nervous system, shown to have a profound effect on neuron growth, synapse growth and health. Research in depression and Alcheimer’s disease revealed disrupted BDNF pattern expression.
- Glial Cell Line-Derived Neurotrophic Factor (GCNF) – this is an exceptionally important, naturally occurring peptide that promotes neuron survival, decreases the loss of neurons and, as some studies have pointed out, has the potential to aid the prevention of Parkinson’s and ALS.
- Ciliary Neurotrophic Factor (CNTF) – this is an interesting hormone affecting the growth of certain neural cells and has been a subject of numerous trials aimed at treating ALS.
- Nerve Growth Factor (NGF) – this is a particularly important peptide which regulates the growth, survival and neuron increase in number. Some studies showed NGF is one of the important factors in programmed cell death and regulation of certain immune system mechanisms.
Looking at these effects, it’s not hard to imagine why scientists used these molecules – to try and merge all these positive effects into one single mix. But were they successful? We actually have some clinical trials atesting to these possibilities:
- Cerebrolysin and Dementia – a study done in 2012 evaluated the outcomes of cerebrolysin therapy in patients with Alcheimer’s over the course of a 12 week treatment period. The study showed significant improvements in cognitive functions and the symptoms of dementia lasting up to several months after the study was finished.
- Cerebrolysin and Parkinson’s – we know that the onset of Parkinson’s disease has to do with the protection of dopamine producing neurons. The loss of these neurons is what leads to motor deficits characteristic for this disease. Unfortunately, we haven’t had human trials, but the one on mice showed that cerebrolysin administration protected these neurons and also lowered certain hormones responsible for Parkinson’s disease worsening.
- Stroke and Brain Injuries – though we don’t have many studies dealing with this topic, some small-scale ones showed cerebrolysin as being not only safe to use, but also helpful in recovery rate if given within 72 hours. Research in infants with brain injury induced communication delay also showed cerebrolysin improved therapeutic outcomes.
Even though these positive effects may seem overwhelming, leaving you wondering why cerebrolysin is not a mainstream, FDA-approved drug still, it’s important to note most of these findings were done on a limited sample (and mostly on animal studies). We have yet to see its effects in large-scale studies and, more importantly, see the long-term benefits of cerebrolysin therapy. Even though the initial results seem promising, we need to be patient and wait for more information before the final verdict.
References:
https://gsrs.ncats.nih.gov/ginas/app/beta/substances/37KZM6S21G%20
Allegri RF, Guekht A. Cerebrolysin improves symptoms and delays progression in patients with Alzheimer’s disease and vascular dementia. Drugs Today (Barc). 2012 Apr;48 Suppl A:25-41. doi: 10.1358/dot.2012.48(Suppl.A).1739721. PMID: 22514793.
Plosker GL, Gauthier S. Cerebrolysin: a review of its use in dementia. Drugs Aging. 2009;26(11):893-915. doi: 10.2165/11203320-000000000-00000. PMID: 19848437.
Masliah E, Armasolo F, Veinbergs I, Mallory M, Samuel W. Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol Biochem Behav. 1999 Feb;62(2):239-45. doi: 10.1016/s0091-3057(98)00144-0. PMID: 9972690.
Ozkizilcik A, Sharma A, Lafuente JV, Muresanu DF, Castellani RJ, Nozari A, Tian ZR, Mössler H, Sharma HS. Nanodelivery of cerebrolysin reduces pathophysiology of Parkinson’s disease. Prog Brain Res. 2019;245:201-246. doi: 10.1016/bs.pbr.2019.03.014. Epub 2019 Apr 2. PMID: 30961868.
Ozkizilcik A, Sharma A, Lafuente JV, Muresanu DF, Castellani RJ, Nozari A, Tian ZR, Mössler H, Sharma HS. Nanodelivery of cerebrolysin reduces pathophysiology of Parkinson’s disease. Prog Brain Res. 2019;245:201-246. doi: 10.1016/bs.pbr.2019.03.014. Epub 2019 Apr 2. PMID: 30961868.
Hassanein SM, Deifalla SM, El-Houssinie M, Mokbel SA. Safety and Efficacy of Cerebrolysin in Infants with Communication Defects due to Severe Perinatal Brain Insult: A Randomized Controlled Clinical Trial. J Clin Neurol. 2016 Jan;12(1):79-84. doi: 10.3988/jcn.2016.12.1.79. Epub 2015 Sep 11. PMID: 26365023; PMCID: PMC4712290.
Metastin or Kisspeptin is believed to have the ability to prevent the spread of cancer or metastasis. This peptide is produced by the hypothalamus, which stimulates the release of GnRH or gonadotropin-releasing hormone, which then causes follicle-stimulating hormone and luteinizing hormone to be released from the purity gland.
Kisspeptin is used in testosterone replacement therapy instead of hCG to increase testosterone levels. That’s why it has emerged as a crucial regulator of the mammalian reproductive axis.
This peptide was first discovered in 1996 when it managed to inhibit melanoma cell lines. It belongs to a family of peptides that are derived from the KISS1/kiss1 gene structure, forming from prepro-kisspeptin, which has differential proteolysis for a common precursor.
Kisspeptin is classified as an RF or neuroactive peptide with a specific Arg-Phe-NH2 motif.
Benefits:
Kisspeptin binds to receptors in the pituitary gland, triggering a response that prompts the gland to release neurotransmitters, signaling the release of LH and FSH.
Based on numerous animal studies, scientists have managed to uncover the following benefits:
- Boosts the production of testosterone naturally
- Regulates fertility
- Increases sexual drive
- Improves immune response
- Boosts brain function
- Promotes weight loss
How does Kisspeptin work?
This peptide stimulates the release of GnRH or gonadotropin-releasing hormone. It enters the purity gland through receptor sites, causing a gland to release neurotransmitters, which later signal the releases of FH and LH. These hormones play a crucial role in the production of oestradiol and testosterone.
Kisspeptin mimics the action of hCG and clomiphene, and according to some animal studies, it can affect fertility in female and male animals.
Distribution of Kisspeptin
Kisspeptin was first found in the placenta, and later, it has been observed in the small intestine, pancreas, ovaries, and testis in mammals. The primary expression of Kisspeptin and its receptors have been shown in two big neuronal populations within the hypothalamus of rodents, the anteroventral periventricular nucleus and the arcuate nucleus.
PeptideShop.com is selling insulin-like growth factor 1 (IGF-1) LR3 in vials of 3mg, in a lyophilized state, and it requires dissolution. Your choice of diluent will depend on the nature of your lab testing, but the most common ones are certainly sterile distilled water, or a sterile dilute acetic acid.
IGF-1 LR3 is based on IGF which has been chemically altered to have a prolonged half-life. This allows it to be more effective and increases the duration of its action.
IGF-1 is a 70 amino acid long peptide chain, similar in structure to insulin, which is able to bind to the insulin receptors found within the body. Insulin-like growth factor 1 is one of the principal mediators of human growth hormone (GH). What this means is IGF-1 plays a crucial role in promoting cell growth, differentiation and has a distinct anabolic effect, especially in adults.
IGF-1 LR3 And Cell Proliferation
Since IGF-1 is a part of a wide growth factor network, it plays a part in cellular proliferation and differentiation, especially in muscles and connective tissue. It also delays cell apoptosis, preventing premature cell death.
The difference between IGF-1 and IGF-1 LR3 variant is, as we said before, LR3’s longer half life; it remains in the bloodstream longer and expresses its action over a longer period.
In vitro medical studies showed that this peptide leads to the increase of muscle cells, not by hypertrophy but by actual cell division. This “side effect” proved of interest in the bodybuilding world where individuals would use (abuse) it to improve their results and get results faster. It came to a point where this peptide was declared a doping agent and banned in different high level sports competitions.
Of course, this is not something we approve of, as we are only selling peptides for laboratory testing.
IGF-1 As A Medical Disease Marker
We’re used to talking about IGF-1 and its LR3 counterpart, in the context of medical therapy and treatment, but its levels might point to a medical problem – deficiency within the body. There are many different reasons for IGF-1 deficiency, but it’s suspected that the main one is GH and growth hormone receptor defects. This is especially common in children where primary IGF deficiency is detected and treated.
IGF-1 LR3’s Effects On Myostatin Regulation
Myostatin is a protein found in muscle tissue of the skeletal system, mainly responsible for hypertrophy and cell division and differentiation. We’re not talking about muscle building here, but normal bodily muscle development during the growth period.
Deficiencies with this hormone will lead to muscle dystrophies, where affected individuals experience muscle loss, decreased quality of life as well as life expectancy. This is why researchers are so hung up on developing a IGF-1 LR3 treatment protocol that would help regulate myostatin protein, prevent muscle loss and improve the quality of life of the patients.
Sadly, we are still in the early stages of testing and research – most commonly used models are animal ones, and we have yet to see the effects of this therapy in humans.
IGF-1 LR3 Effects On Cell Aging
In addition to cell proliferation, differentiation and wound healing, some animal studies showed IGF-1 LR3 affects cellular longevity (by protecting them and prolonging apoptosis).
Besides general wellbeing, this therapy can be aimed at slowing down the progression of deteriorating diseases such as dementia or muscle dystrophy. These results have been reported in mice studies, but we should move into human testing soon.
References:
Bailes J, Soloviev M. Insulin-Like Growth Factor-1 (IGF-1) and Its Monitoring in Medical Diagnostic and in Sports. Biomolecules. 2021 Feb 4;11(2):217. doi: 10.3390/biom11020217. PMID: 33557137; PMCID: PMC7913862.
Ipamorelin is a pentapeptide that showed a significant growth hormone secretion potential both in vitro and in vivo studies. In vivo studies, it showed a similar potency and effectiveness as GHRP-6 (a synthetic growth hormone-releasing hexapeptide) as it stimulates GH release via the GHRP receptors.
What’s interesting about ipamorelin is that it did not raise ACTH (Adrenocorticotropic hormone) nor cortisol level significantly; something we’ve seen happening with GHRP-6 and GHRP-2. So, we can conclude that ipamorelin is the first GHRP-receptor agonist with GH release selectivity similar to GHRH. This is why ipamorelin is an interesting candidate for further testing.
In addition to stimulating GH secretion, this peptide has seen some interesting use in the treatment of postoperative ileus (POI), a condition characterized by transient loss of gastrointestinal motility following abdominal surgery.
The exact mechanism behind POI is a complex one, involving many different bodily structures; in addition, condition is often worsen due to the opioid drugs used for patient pain management.
In rodent studies, ipamorelin was found to selectively stimulate ghrelin (hormone produced by our stomach, affecting food intake, deposition and growth hormone release) without raising cortisol or adrenocorticotropic hormone levels. These effects were shown in both lower GI tract as well as the upper, making this peptide a viable candidate for potential POI treatment.
References:
Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822.
Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012 Oct 19;4:149-55. doi: 10.2147/JEP.S35396. PMID: 27186127; PMCID: PMC4863553.
Cagrisema 10mg is one of the latest PeptideShop’s peptide blends, which combines cagrilintide and semaglutide. Each vial contains a combination of lyophilized cagrilintide and semaglutide, 5mg each, tested for purity and strength, and suitable for lab experiments and chemical trials.
Semaglutide is a GLP-1 receptor agonist. GLP-1 is one of the main gut peptide hormones in humans, which plays a role in many different mechanisms within the body from insulin secretion, glucagon release, gastric emptying, appetite and energy intake.
And cagrilintdide is an amylin analogue co-secreted with insulin, which plays a role in glycemic control and gastric emptying.
Researchers hypothesize that this combination profoundly influences receptor changes in the brain, insulin secretion, appetite regulation and glucagon secretion.
Though this combination has not yet been fully tested, we have data from a study on the effects of Cagrisema on patients with type 2 diabetes.This was a 32-week, double-blind study across 17 sites in the USA, conducted on 92 individuals in total.
Final results showed that cagrisema resulted in clinically relevant improvements in glycaemic control (significant change in HbA1c) and, more importantly, a greater weight loss versus semaglutide as well as cagrilintide.
References:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01163-7/abstract
Retatrutide is one of the latest incretin mimetic drugs being tested for their weight reduction properties. Researchers use incretin mimetic agents as they work to mimic incretin hormones (gut peptides that get secreted after we eat) to allow for a better insulin secretion and hyperglycaemic control.
Even though there are numerous weight reduction agents being prescribed and used, FDA-recognized “treatment” for nonsyndromic obesity are:
- Orlistat
- Phentermine-topiramate
- Naltrexone‐bupropion
- Liraglutide and
- Semaglutide
With the exception of glucagon-like peptide 1 receptor agonists (such as semaglutide), most weight reduction agents come with a specific set of side effects such as nausea, gastrointestinal distress, abdominal pain, vomiting, diarrhea, or a general weight decrease that does not cross the 15% mark. Some of these medications even come with a warning against using them if a patient is suffering from a kidney, heart, thyroid or any related problems.
This is why scientists are turning more and more to retatrutide, because this incretin mimetic decreases appetite, promotes the feeling of fullness and slows down the process of gastric emptying, but does all that while presenting with minimal side effects and increased weight loss effectiveness, compared to liraglutide or semaglutide.
Retatrutide Mechanism of Action
Retatrutide exerts a powerful glucagon-receptor agonistic effect. When we compare it to human glucagon and glucagon-like peptide 1 (GLP-1), it exhibits:
- Reduced potency on the GCGR (human glucagon receptor) and GLP-1R (glucagon-like peptide-1 receptor)
- Enhanced potency at the human GIPR (gastric inhibitory polypeptide receptor)
When talking about in vitro experiments, retatrutide demonstrated similar efficacy in evoking glucose production within hepatocytes and inducing lipolysis. Also, retatrutide showed a favorable half-life of 6 days, enabling it a weekly dosage regimen (should the drug get FDA approved).
Another double-blind study conducted in the US on obese patients showed promising results. 338 adults in total were involved, split into 6 cohorts (depending on the weekly dosage), up against a placebo group. Retatritude group experienced the following results:
- 1mg group – after 24 weeks this group experienced weight loss of 7.2%, and after 48 weeks a total loss of 8.7%
- 4mg group (commencing with 2mg) – after 24 weeks this group experienced a weight loss of 11.8%, and after 48 weeks a total loss of 16.3%
- 4mg group (commencing with 4mg) – after 24 weeks this group experienced a weight loss of 13.9%, and after 48 weeks a total loss of 17.8%
- 8mg group (commencing with 2mg) – after 24 weeks this group experienced a weight loss of 16.7%, and after 48 weeks a total loss of 21.7%
- 8mg group (commencing with 4mg) – after 24 weeks this group experienced a weight loss of 17.9%, and after 48 weeks a total loss of 23.9%
- 12mg group (commencing with 2mg) – after 24 weeks this group experienced a weight loss of 17.5%, and after 48 weeks a total loss of 24.2%
In contrast, the placebo group only experienced a 1.6% weight loss after 24 weeks and 2.1% after 48. Findings also showed that adverse effects related to retratitude treatment (such as nausea, vomiting, diarrhea and constipation), were mild and depended on the dosage.
In conclusion, this peptide showed promising results in addressing obesity in both in vitro and human test subject studies. However, test samples were relatively small, and we still need more research and clinical trials to show the effectiveness of retratutide as an effective, long-term way of managing weight.
Reference:
Naeem M, Imran L, Banatwala UESS. Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence. Health Sci Rep. 2024 Feb 5;7(2):e1864. doi: 10.1002/hsr2.1864. PMID: 38323122; PMCID: PMC10844714.
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