NOOPEPT GVS-111 POWDER (10 GRAMS)

Description

Noopept GVS-111 Nootropic Powder

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?

N-phenylacetyl-L-prolylglycine ethyl ester, GVS-11, also referred to as Noopept 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 was found to normalize impaired behavior related to cerebral ischemia while preventing the accumulation of lipid peroxidase byproducts and inhibiting antioxidant systems in the brains of rats with varying sensitivity levels of hypoxia.

2) 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.

 

Selected Data

1) The research team of Zarubina et al studied the effects of Noopept on functional and metabolic brain impairments in animals with both high and low sensitivity to hypoxia under chronic ischemic conditions. For the purpose of this study 112 male Wistar rats weighing 160-180 grams were utilized. The animals were divided into treatment groups based on their sensitivity to acute hypoxia by placing them in a pressure chamber elevated to a height of 12,000 meters at velocity of 50 meter/second. The rats were exposed to this height until agonal respiration emerged. Rats enduring the hypoxic conditions for 5-10 minutes were placed in the low sensitivity group and rats that endured the hypoxic conditions for longer than 10 minutes were placed in the high sensitivity group [2].

Cerebral ischemia was then induced by occluding the common carotid arteries while the followed by assessing the neurological status using the McGrow stroke index. In addition to the stroke index muscle tone of the animals was evaluated through a self-pulling-up test using a horizontal beam at a height of 30 cm above a stable surface. Immediately after occlusion of the cerebral arteries 0.5 mg/kg of Noopept was dissolved in saline and intraperitoneally injected into the rats. Experimental treatment with the nootropic occurred daily for 7 days.

An open field test and elevated plus-maze tests were used to examine the physiological reactions of the rats, while the orientation, exploratory, emotional, stereotypical and motor components were assessed using the rodent behavioral atlas. 7 days after induction of cerebral ischemia, cognitive functioning was evaluated through the conditioned passive avoidance reflex (CPAR) as an indicator of depressive behavior. Antidepressant effects of Noopept were further examined 1 day after CPAR evaluation in the behavioral despair test. Levels of unsaturated fatty acids conjugated dienes and ketotrienes and malondialdehyde were assessed as indicators of the intensity of free-radical process in the brain. Superoxide dismutase activity, content of reduced glutathione, protein SH groups, and fat soluble antioxidants levels were also evaluated as indicators of the functionality of the antioxidant system of the brain [2].

2) 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].

 

Discussion

1) The results of the study conducted by Ostrovskaya et al found that rats with varying sensitivity to hypoxia exhibited significantly different behavior reactions based on the data collected from the open field test and the elevated plus-maze test. The animals with a low sensitivity to hypoxia exhibited steady state behavior while the animals with a high sensitivity to hypoxia exhibited pronounced exploratory and locomotor activity, as well as increased anxiety. During the postischemic period, spontaneous motor activity was found to reduce in rats included in both the high sensitivity and low sensitivity experimental groups. Highly sensitive rats lost their capacity for exploratory activity, indicating disintegration of some of the integral behavioral reactions, while low sensitivity rats retained some behavioral elements such as sniffing, excursion to center field, and on the spot movements [2].

Rats that were highly sensitive to hypoxia experienced reduced autonomic manifestations of emotions indicated by a reduced number and duration of grooming acts and reduced boluses and defecation acts. On the other hand, in rats with low sensitivity to hypoxia there was an increase in emotional status. However, rats in both groups experienced high levels of anxiety represented by shorter amounts of time spent in open maze arms, peeking out from closed shelves, short ventures to the center of the apparatus, and peering down from the edges of the maze. It is important to mention that these behaviors were more prevalent in the rats with high sensitivity to hypoxia [2].

Additionally, both high and low sensitivity animals exhibited longer periods of duration during Porsolt’s test, as well as reduced active swimming. These findings are consistent with the formation of depression. The inhibition of orientation, exploratory activity, and reduced mobility acted as representations of stressful situations and was associated with increased emotional reactivity and anxiety.CPAR was reproduced 24 hours after training took place, and revealed that 80% of both low and high sensitivity rats were familiar with the electric current stroke and did not enter the dark cage during the entire observation period. The other 20% of the rats eventually entered the dark cage after a long latency period. Following occlusion of the carotid arteries there was a significant reduction in the CPAR latency period in both groups of rats. It was mentioned that the impairments in cognitive functioning were more pronounced in the group of animals with a high sensitivity to hypoxia [2].

Figure 1: Changes in A) active swimming; B) passive swimming; and C) immobility in rats after induction of cerebral ischemia. 1) response to sham-operation in low and high sensitivity groups; 2) response to induced ischemia in low and high sensitivity groups; and 3) response to Noopept treatment in low and high sensitivity groups with induced ischemia

7 days after the carotid arteries were occluded, neurological impairments of varying severities were rated on a scale of 0.5 to 12. 0.5-2.5 points was classified as slight neurological symptoms, 2.5-5.5 was classified as medium neurological symptoms, and 5.5-12 points was classified as severe neurological symptoms. 95% of the control group of rats experienced severe or medium-severe cerebral ischemia following occlusion of the carotid arteries. Neurological disorders characterized by manege movements, pareses, and palsy were observed in 45% of low sensitivity rats and 60% of high sensitivity rats, 30% of low sensitivity rats and 40% of high sensitivity rats, and 10% of low sensitivity rats and 20% in high sensitivity rats, respectively.

By day 3 after occlusion of the carotid arteries 45% of low sensitivity rats and 30% of high sensitivity rats had survived. However, after the animals were treated with Noopept, the survival rate of both low and high sensitivity rats increased to 84% and 76%, respectively. Administration of Noopept was found to reduce manifestations of neurological deficits. The number of manege movements exhibited by the rats significantly decreased while the animals also developed no pareses of the limbs or palsy. Locomotion, orientation, and exploratory behaviors were also increased in the rats with low and high sensitivity to hypoxia, suggesting that the integral behavioral reactions of the animals were recovered [2].

Figure 2: Changes in A) inert movements, B) limb weakness, and C) manege movements in rats 3 days after induction of cerebral ischemia. 1) response to ischemia in low and high sensitivity groups and 2) response to Noopept administration in low and high sensitivity groups

Noopept was also found to correct the emotional status of animals while also reducing anxiety levels in the animals. Administration of the treatment also restores cognitive functioning by improving training capacity and preserving memory that was lost as a result of the induction of cerebral ischemia. Seven days of treatment with Noopept allowed the animals to accurately remember the delivery of a painful stimulus upon entry into a dark cage, leading to increased latency periods. Swimming and immobilization durations were also found to be significantly improved in both low and high sensitivity rats suggesting that the compound elicits pronounced antidepressant effects [2].

Occlusion of the carotid arteries was associated with reduced activity of antioxidant systems as well as an accumulation of lipid peroxidase byproducts in brain tissues. After assessing changes in the levels of lipid peroxidation by products and various endogenous antioxidant levels, the level of byproducts identified in the brain of high sensitivity rats was greater than the amount of byproducts found in the brains of low sensitivity rats. These changes peaked on day 3 after occlusion of the carotid arteries and persisted until day 7. Similar to previous findings of the study, these results were more pronounced in the group of rats with a high sensitivity to hypoxia [2].

Treatment with Noopept was found to significantly reduce levels of conjugated dienes, ketotrienes, malondialdehyde, and increase activity of superoxide dismutase. The researchers noted that this result could potentially be due to the activation of antioxidant system activation leading to decreased generation of lipid peroxides. Following treatment, accumulation of lipid peroxidase byproducts and suppression of activity of antioxidant systems was prevented in a group dependent-manner respective to both high and low sensitivity groups.

The researchers were able to conclude that treating rats with high or low sensitivity levels to hypoxic conditions with Noopept for 7 days following the occlusion of the common carotid arteries and onset of neurological deficits, had the ability prolong survival, increase locomotor, orientation, and exploratory activity, and restore emotional status of the animals. In addition to preventing suppression of antioxidant system activation and the accumulation of lipid peroxidase byproducts, Noopept treatment reduced levels of depression and anxiety in the animals and improved their training capacity [2].

2) 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].

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].

 

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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