NOOPEPT GVS-111 30ML LIQUID (30MG/ML, 900MG BOTTLE)

Description

Noopept GVS-111 Nootropic Liquid

CAS Number	157115-85-0
Other Names	Omberacetam, GVS-111, GVS 111, ethyl phenylacetyl-Pro-Gly, UNII-4QBJ98683M, 4QBJ98683M, SCHEMBL194807, CHEMBL4303687, DTXSID80166214
IUPAC Name	ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate
Molecular Formula	C₁₇H₂₂N₂O₄
Molecular Weight	318.4
Purity	≥99% Pure (LC-MS)
Liquid Availability	30mL liquid (30mg/mL, 900mg bottle)
Powder Availability	10 grams
Gel Availability	N/A
Storage	Store in cool dry environment, away from direct sunlight.
Terms	All products are for laboratory developmental research USE ONLY. Products are not for human consumption.

 

What is Noopept?

Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-11) is a nootropic dipeptide compound derived from nonpeptide prototypes of piracetam and vasopressin. Noopept has been shown to promote neuroprotection and elicit several positive effects related to blood glucose regulation, body weight changes, and antidiabetic activity. The mechanism of action behind the nootropic is related to its ability to block voltage-dependent calcium and calcium-dependent potassium channels, as well as increase levels of neuron growth factor (NGF) and brain-derived neurotrophic growth factor (BDNF). Additionally, Noopept has been found to regulate antioxidant enzymatic activity and lipid peroxidase activity. Current research is focused on further defining the benefits derived from the compound and clarifying the effects of the nootropic on puberty and reproductive organ integrity [1].

 

Main Research Findings

1) Noopept has the potential to elicit positive effects in cases of pubertal diabetes as treatment with the nootropic was found to normalize delayed puberty while decreasing blood glucose levels and insulin resistance.

2) Treatment with Noopept has been found to elicit neuroprotective effects on the expression of mRNA for neurotrophic factors BDNF and NGF.

 

Selected Data

1) In order to assess the several benefits elicited by Noopept in a prepubertal type 1 diabetes model, the research team of Gürbüz et al utilized 60, prepubertal, 28 day old male Sprauge Dawley rats. The animals were housed 5 rats to cage and maintained under standard laboratory conditions with ad libitum access to food and tap water. The rats were randomly divided into 6 experimental treatment groups including: 1) the control group, 2) the diabetes control, 3) the Noopept control, 4) diabetes and Noopept treatment, 5) diabetes and insulin treatment, and 6) diabetes with Noopept and insulin treatment [1].

Type 1 diabetes mellitus was induced in the experimental groups through an intraperitoneal injection of 50 mg/kg STZ, dissolved in a sodium citrate buffer, administered after 12 hours of fasting. The rats were considered diabetic if their fasting blood glucose measured > 200 mg/dL after 3 days. After the diabetic experimental groups were identified, Noopept in a 0.5 mg/kg dose, or insulin detemir in a 1U long-acting dose were dissolved in physiological serum and injected intraperitoneally, daily for 14 days. For the control groups of rats, saline was injected intraperitoneally. 30-60 minutes after all treatments were administered to the test subjects, the animals underwent the Morris water maze test in order to examine changes in their cognitive functioning [1].

The Morris water maze tests included a 150 cm diameter apparatus that is 60 cm in height and filled up to 40 cm with water. Nontoxic black dye was added to the water to make it opaque so the rats were not able to see the bottom of the tank while the surface of the water was divided into 4 equal quadrants. The northwest quadrant was determined as the target destination where a platform was placed 30 cm away from the edge of the northwest quadrant and hidden 2 cm below the surface of the water. A fibrous black cloth was placed over the platform in order for the rats to grip their claws on in order to feel safe. Over a 4 day learning period the platform was kept in the same position and the animals were trained to locate it while the amount of time it took was measured by the research team [1].

Each trial took place over 20 minutes and the rats were placed in different quadrants of the maze and allowed to swim around for 90 seconds in order to find the platform. If the rats were unable to find the platform they were gently placed onto it and remained there for 30 seconds. On day 5 of the experiment the probe test was performed and the platform was removed from the apparatus. Each test subject was placed in the opposite corner of the apparatus from where the platform was previously located. A computerized video camera was used to monitor and record the distance of the animal, as well as the amount of time each animal spent in the quadrant where the platform was previously located [1].

In addition to the Morris water maze test, blood glucose and body weight measurements were obtained on day 0 prior to the STZ injection, day 3, day 10, and day 17 of the experiment. Additionally, on the 11th day of the experiment (postnatal day 39) prepuce-glans penis separation was examined in order to define the pubertal process, while insulin resistance was calculated by the homeostasis model assessment of insulin resistance. On the 18th day of the experiment (postnatal day 46), the animals were euthanized using 70 mg/kg of ketamine and 8 mg/kg xylazine anesthesia after collecting blood samples from heart tissue. Tissues from the hippocampus, the hypothalamus, and the testis were all dissected from the rats and preserved using 10% formaldehyde and embedded in paraffin for further histological analysis [1].

Tissue sections were sliced and mounted on slides, followed by staining with hematoxylin-eosin. For the stained hippocampal sections, the researchers randomly selected to count the total number of neurons from 3 areas in the pyramidal layer of the CA1 region. Neurons with round and light nuclei were defined as normal while shrunk neurons with picnotic nuclei were defined as degenerated. Tissues collected from testicular regions were assessed for cell stability, congestion, vacuolization or edema in the interstitial tissue, spilled cells in the tubules, cell infiltration, mean seminiferous tubular diameter, and germinal epithelial cell thickness. It is important to note that the diameter of 20 separate seminiferous tubules were randomly selected to measure [1].

Immunohistochemical analysis took place by slicing 4 micrometer thick tissue sections that were then deparaffinized, rehydrated, placed in an antigen retrieval solution composed of a citrate buffer, boiled in a pressure cooker for 20 minutes, and allowed to cool to room temperature for an additional 20 minutes. The slides were then washed with phosphate buffer saline and incubated in a hydrogen peroxide solution for 15 minutes in order to block endogenous peroxidase activity. The blockage was achieved by applying non-specific antigen-binding sites with a protein block, primary antibodies that do not result in cross-reactivity in the test subjects, and polyclonal GnRH antibodies, for 60 minutes [1].

After 60 minutes the sections were rinsed again with phosphate buffer saline, followed by incubation with streptavidin peroxidase and biotinylated secondary antibody for 10 minutes. The samples were assessed by the research team using chromogenic substrates AEC, followed by counterstaining with hematoxylin and mounting on a glass slide. Immunoreactivity was assessed by observing brown staining in the neuron bodies following application of GnRH and Kp to the hypothalamus sections. The arcuate nucleus of the hypothalamus was evaluated for Kp while the prevalence and severity of the staining immunoreactivity were scored semiquantitatively. That being said, the product of staining immunoreactivity prevalence x staining immunoreactivity severity was defined as the total staining score [1].

Additionally, ELISA rat kits were used to measure levels of insulin, follicle-stimulating hormone, luteinizing hormone, BDNF, and NFG. A 5 mg sample of the deep freezed left hemisphere of the hippocampus was put into a glass tube with 2 ml of phosphate buffer and homogenized for 3 minutes. The obtained homogenates were used to measure levels of NGF and BDNF in the tissues via ELISA testing, while protein levels were used to calculate levels of insulin, follicle-stimulating hormone, and luteinizing hormone from serum samples [1].

2) The research team of Ostrovskaya et al examined the effects of a single treatment of Noopept and long term treatment with Noopept, on the expression of the neurotrophic factors BDNF and NGF due to their association with the development of Alzhiemer’s disease. For the purpose of this study, male outbred albino rats each weighing 240-300 grams each were obtained from a Stolbovaya nursery and utilized. Animals were housed 6-8 rats per cage and maintained under standard laboratory conditions with free access to food and water [2].

All of the test subjects were randomly divided into 4 different experimental treatment groups including: 1) rats receiving a single intraperitoneal injection of 0.9% NaCl; 2) rats receiving a single intraperitoneal injection of a 0.5 mg/kg dose of Noopept; 3) rats receiving 28 days of treatment with 0.9% NaCl; and 4) rats receiving 28 days of treatment with 0.5 mg/kg Noopept. 30 minutes after the single dose of treatment was administered to groups 1 and 2 and 30 minutes after the final dose of treatment was administered on day 28 to groups 3 and 4, the animals were euthanized and the brain was removed in order to dissect the cerebral cortex and the hippocampus. The sections were immediately placed in liquid nitrogen in order to preserve the tissues for further evaluation [2].

A TRYzol reagent was used to isolate total RNA while the quality of the isolation and the RNA concentration was estimated using light absorption at both 260 and 280 nm. 2 micrograms of RNA was obtained from each sample and the RNA was separated using a denaturing agarose gel in combination with 10% formaldehyde. The membranes were washed, exposed, and stained with methylene blue prior to hybridization in order to measure RNA concentrations in the sample. Target mRNA concentrations in the samples were equalized by the total RNA concentration and the values were normalized in accordance to the control values. Next, DNA probes for hybridization complementary to NGF and BDNF gene sequences were labeled and synthesized using NGF and BDNF primers [2].

 

Discussion

1) As it was previously mentioned, blood glucose and body weight changes were measured in all groups on experimental days 0, 3, 10, and 17. The control group of rats was found to experience significantly more weight gain in comparison to the diabetes control group, the Noopept control group, the diabetes and Noopept group, and the diabetes, Noopept, and Insulin group. Additionally, there were no significant changes in body weight gain when comparing the control group and the diabetes and insulin group. In terms of blood glucose changes, levels were found to increase in all diabetic experimental groups by day 3. There were no significant changes in blood glucose levels measured on days 3, 10, and 17 between the diabetes control group and the diabetes and insulin group. However, the blood glucose levels of both the diabetes and Noopept group and the diabetes, Noopept, and insulin group were found to be significantly decreased by day 17 in comparison to levels measured on day 3 [1].

When looking at changes in levels in insulin and insulin resistance, insulin in the diabetes control group of rats was significantly higher than the diabetes, Noopept, and insulin group of rats by the end of the experiment. Similar results were seen in terms of insulin resistance. Insulin resistance in the diabetes control group of rats was higher than compared to the other experimental treatment groups, most notably, the diabetes Nootropic, and insulin group of rats. The insulin resistance in the diabetes, Nootropic, and insulin group was also markedly lower than the diabetes and insulin treatment group [1].

The Morris water maze test was performed as an assessment of cognitive functioning and memory in the rats. The results reported that there were no significant differences in the platform finding time measured in each experimental group. However, it is important to mention that while the findings compared between each group was not considered significant, the diabetic groups treated with Noopept and/or insulin generally had lower finding times than the diabetes control group of rats. Additionally, when comparing the area swam until finding the platform, the area swam in the platform quadrant, and the distance to the platform at the end of the trial, there were no statistically significant differences in the values between the experimental treatment groups [1].

Histological findings related to samples collected from the testis reported that the testicular tissue of the healthy control groups had a normal appearance. However, in the testicular tissue collected from the diabetes control group of rats, cell stability in the mitotic phase, congestion, vacuolization or edema in the interstitial tissue, spilled cells in the tubules, and cell infiltration were all observed. These changes identified in the testicular tissue were found to be significantly reduced in the diabetic groups treated with Noopept and insulin. Histological findings related to samples collected from the hippocampus found that the diabetes control group of rats experienced neuronal degenerative changes and decreased neuronal density, in comparison to the control group. Neuronal degeneration in the diabetic groups was found to significantly reduce in the diabetes and Noopept group, the diabetes and insulin group, and the diabetes, Noopept, and insulin group. There was a statistically significant difference between the diabetes and Noopept group in comparison to the diabetes control group of animals [1].

The diameter of the seminiferous tubules and the germinal epithelial cell thickness of each testis from the different experimental treatment groups were measured and determined in units of micrometers. There were notable differences in the measurements between the diabetes control group and the treated groups. Measurements collected from the animals that received either Noopept or insulin were similar among the groups, however, when Noopept and insulin were delivered in combination with each other there were significant differences between the measurements of the seminiferous tubules and germinal epithelial cells. Additionally, when determining the rate of puberty, by the end of the experiment, 7 of the rats in the diabetes control group and 2 of the rats in the diabetes and insulin group had not entered puberty. It was also mentioned that when assessing levels of NGF and BDNF, there were no significant differences in the levels among the experimental groups [1].

When assessing the immunohistochemical findings obtained from the hypothalamus sections, there were no significant changes observed between the experimental groups. It was noted that when comparing the diabetic groups of animals, GnRH immunoreactivity of the diabetes and Noopept group of rats was significantly higher than the diabetes, Noopept, and insulin group of rats, at a level similar to that of the control group of rats. Additionally, there was no statistically significant difference in Kp immunoreactivity in the hypothalamic arcuate nucleus. There was also no noticeable difference in levels of luteinizing hormone and follicle-stimulating hormone between the different experimental treatment groups [1].

Overall, the research team of Gürbüz et al concluded that Noopept elicits several benefits when managing pubertal type 1 diabetes mellitus. However, further studies should be conducted regarding modulation of the treatment in order to prevent chronic complications. Investigation regarding the mechanism of action behind the cellular effects of Noopept should also be completed in order to compare the nootropic to other diabetes drugs. Protein expression of NGF and BDNF proteins should be researched as well in order to improve molecular mechanisms at the receptor and mRNA levels to improve the efficacy of Noopept in treating cognitive deficits and neurodegeneration [1].

2) When evaluating the expression of the neurotrophic factors NGF and BDNF, the researchers reported that expression in the cerebral cortex was found to slightly decrease after a single dose of Noopept was administered. However, when Noopept was administered to the animals daily, for 28 days, there was a noticeable increase in the expression of BDNF. 28 days of treatment with the nootropic also resulted in a greater increase in neurotrophic factor mRNA expression in the hippocampus of the rats. It was mentioned that NGF mRNA expression increased significantly more in comparison to BDNF mRNA expression. These findings suggest that long term administration of Noopept may improve neuronal recovery as it does not lead to the development of a tolerance but rather continues to prompt the neurotrophic effects [2].

Figure 1: Effects of administration of a single dose of Noopept in comparison to 28 days of treatment with Noopept on NGF and BDNF mRNA expression. I is representative of experimental groups 1 and 3, II is representative of experimental group 2, and 3 is representative of group 4.

The reported results of this study indicate that Noopept has the potential to increase the expression of different neurotrophic factors related to neuroprotection and cognitive functioning. The dramatic increase in the neurotrophic factor expression caused by long term treatment with Noopept suggests that the nootropic may enhance the reparative phase of healing after brain trauma. These findings extend on previous research related to the clinical application of Noopept that shows the nootropic elicits cholinosensitizing effects, increases the production of beta-amyloid antibodies, and protects neurons from lipid peroxidation products and accumulation of excessive amounts of pro-inflammatory cytokines. Due to the rapid development of research surrounding the uses of Noopept, there is a newfound potential that the compound may prevent the development of Alzheimer’s disease in subjects experiencing mild cognitive impairments [2].

 

Disclaimer

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

 

Citations

[1] Gürbüz P, Düzova H, Yildiz A, Çakan P, Kaya GB, Bağ HGG, Durhan M, Gül CC, Taşlidere AÇ. Effects of noopept on cognitive functions and pubertal process in rats with diabetes. Life Sci. 2019 Sep 15;233:116698. doi: 10.1016/j.lfs.2019.116698. Epub 2019 Jul 26. PMID: 31356906.

[2] Ostrovskaya RU, Gudasheva TA, Zaplina AP, Vahitova JV, Salimgareeva MH, Jamidanov RS, Seredenin SB. Noopept stimulates the expression of NGF and BDNF in rat hippocampus. Bull Exp Biol Med. 2008 Sep;146(3):334-7. doi: 10.1007/s10517-008-0297-x. PMID: 19240853.

Mechanisms and Effects of Noopept

N-phenylacetyl-l-prolylglycine ethyl ester, more commonly referred to as Noopept or GVS-111, is an ampakine nootropic closely related to the racetam compound, Piracetam. Originally discovered in 1996 by Russian pharmaceutical company JSC LEKKO Pharmaceuticals, Noopept is not considered a true racetam despite its many similarities to racetam compounds. This is due to the absence of a 2-oxo-pyrrolidine core.

Noopept typically works by increasing levels of cycloprolylglycine (CPG) in the brain. CPG is considered a dipeptide composed of proline and glycine and is shown to regulate function of the AMPA receptors and acetylcholine transmission. Ampakine nootropics have a stimulatory effect without many of the side effects that come with long term usage of stimulants. That being said, Noopept has shown promise in enhancing many aspects of cognition and reducing anxiety levels.

Noopept regulates the activity of AMPA and NMDA receptors in the brain, both of which are involved with the utilization of calcium and glutamate in the brain. Because of its ability to modulate the amount of glutamate in and between neurons, Noopept is capable of preventing glutamate toxicity. This also influences long-term potentiation and improves neuroplasticity in the brain, supporting the claim that Noopept is capable of enhancing cognition through memory retention and learning skills.

In addition to regulating AMPA and NMDA receptors, Noopept tends to increase the levels of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Both of these compounds also work to promote neuroplasticity and help replace damaged brain cells, leading to overall better brain health and cognition. A study conducted by Ostrovskaia et. Al examined the effects of administering 0.5 mg/kg of Noopept over 28 days. The results found that this course of treatment led to a decrease in MAPKs and stress-induced kinases as well as an increase in the expression of BDNF and NGF in the hippocampus and hypothalamus of rats (https://pubmed.ncbi.nlm.nih.gov/21395007/). Evidence also shows that the Noopept increases alpha and beta brain waves in order to enhance neuron signaling and communication.

Noopept has also shown promise in reducing anxiety. This is primarily due to the compound’s ability to stimulate D2 and D3 dopamine receptors and acetylcholine nicotinic receptors. Furthermore, research has found that Noopept could potentially regulate various receptors throughout the serotonergic system. These qualities combined lead researchers to believe that the nootropic has the potential to improve mood and reduce anxiety.

 

Noopept vs Piracetam

As it was previously mentioned, Noopept is incredibly similar to the popular racetam nootropic, Pircetam. Both compounds are capable of enhancing cognition and exhibit anti-anxiety and neuroprotective qualities. Noopept and Piracetam are also involved in improving learning and memory and reducing brain damage.

The primary difference between the two nootropics comes from their potency. Noopept is considered approximately 1000 times more potent than Piracetam. Doses of Noopept range from 10-30 mg while doses of Piracetam range from 3000-4000 mg. Another key difference between the two is the extent to which they affect memory. Piracetam helps to facilitate memory retention primarily in the early stages, while Noopept is able to influence not only memory retention, but memory consolidation and retrieval as well. Noopept also has additional anxiolytic qualities than Piracetam does. This is due to Noopept’s known anti-inflammatory and antioxidant properties, as well as its ability to decrease neurotoxicity by regulating levels of glutamate and calcium (https://nootropicsexpert.com/noopept/#_ednref9).

 

Noopept Promotion of Learning and Memory in Lobotomized Rats

A study conducted by Ostrovskaya et. Al provides evidence for the claim that Noopept drastically affects learning and memory. The rats in the first portion of the experiment were taught an active avoidance test before undergoing a bilateral frontal lobectomy (BFL). The second portion of the experiment assessed the habituation of rats in an open field and a passive avoidance test prior to receiving a BFL.

After the BFL the rats were tested again in the active avoidance test, open field, and passive avoidance test. Results found that undergoing a BFL dramatically decreased performance on the active avoidance test, the horizontal activity in the open field was disturbed, and there was diminished latency during the passive avoidance test. Following the operation the researchers administered a 0.5 mg/kg/day of Noopept for 9 days. This method of dosage was found to drastically increase habituation of horizontal activity in the open field test as well as performance levels on both the active and passive avoidance tests (https://pubmed.ncbi.nlm.nih.gov/9833021/).

The nootropics sold by Umbrella Labs are sold for laboratory research only. The description above is not medical advice and is for informative purposes only.

Noopept GVS-111 is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.

 

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