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Noopept is a cycloprolylglycine-derived nootropic peptide that is related to the Racetam class of compounds. Researchers have described it as exhibiting a potency 1000x greater than that of Piracetam.
It enhances cholinergic neurotransmission, heightens synaptic plasticity and is a more powerful anti-oxidant than Piracetam or Vitamin E.
The mechanism of action is not fully understood and research into Noopept is ongoing. Like the Racetams, Noopept appears to positively modulate acetylcholine neurotransmission.
It is observed to increase expression of both NGF and BDNF concentrations in the hippocampus. [4] This may explain why improvements in memory are more apparent following long-term dosage administrations.
Noopept is further reported to reduce depression and anxiety in both human and animal studies. [2]
Additional reported effects include:
- Improves memory function in impaired individuals.
- Increases NGF and BDNF levels.
- Significant neuroprotective and anti-oxidant effects.
- Reduces anxiety, fatigue and irritability while improving mood, sleep and wakefulness.
- Reduces depression and eliminates learned helplessness.
Product Name: Noopept (GVS-111)
Chemical Name: N-phenylacetyl-L-prolylglycine ethyl ester
Formula: C17H22N2O4
Molecular Weight: 318.367 g/mol
CAS Number: 157115-85-0
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Related Topics
- What is Noopept?
- User Reviews
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- How it Works
- Negative Side Effects
- Typical Experiences
- Recommended Dosage
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- Purchasing Guide
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- Is Noopept Legal?
- Comparison to Piracetam
- Comparison to Aniracetam
- Comparison to Oxiracetam
- Comparison to Pramiracetam
Noopept (Neuropept, GVS-111) is also known as N-phenylacetyl-L-prolylglycine ethyl ester.
It is a nootropic peptide with therapeutic effects that are similar to Piracetam, but said to be 1000x more potent. [2]
Noopept was first developed by JSC LEKKO Pharmaceuticals in Russia in 1996 as a prodrug of the endogenous neuropeptide cycloprolylglycine. [1]
It is a dipeptide conjugate of Piracetam and is often classified alongside the Racetam nootropics even though it lacks the 2-oxo-pyrrolidone base structure.
Noopept is noted for its neuroprotective properties which include an anti-oxidant and anti-inflammatory effect as well as the ability to prevent neuro-toxicity caused by excessive calcium and glutamate.
Studies have found it to exert a positive impact on memory formation, consolidation and retrieval. [2] It has also been found to possesses an anxiolytic effect as well mild psychostimulant-like effects. [3]
Noopept Chemical Structure
Noopept or N-phenylacetyl-L-prolylglycine ethyl ester is a synthetic dipeptide molecule with a chemical structure similar to Piracetam.
It is derived from the endogenous dipeptide Cycloprolylglycine which is a combination of the amino acids glycine and proline in a cyclic configuration. [1]
Because it does not have a 2-oxo-pyrrolidone nucleus, it is not technically a racetam nootropic. However, many researcher group it into this family given its similar mechanism of action.
Noopept Pharmacokinetics
Noopept has excellent penetration of the blood-brain barrier. In rat trials following oral dosages, there was almost no difference between blood serum and neural concentrations of Noopept.
Following a 50mg/kg oral dosage of Noopept, the serum (blood) Tmax was measured at 0.116 hours with a Cmax of 0.82mcg/mL. After the same oral dosage, brain concentrations were measured with a Cmax 1.289mcg/mL at a Tmax of 0.115 hours. [5]
This result led Boiko et al to conclude that Noopept, “is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an unmodified state” in rats. [5]
In humans, Noopept is typically taken via oral or sublingual administration.
The majority of animal trials have examined the effects of Noopept using injection as the method of administration.
Preliminary findings suggest that oral doses of 50mg/kg are roughly equivalent to injected dosages of 5mg/kg based on serum concentrations and excretion kinetics. [5] This implies that oral bio-availability is only 10% compared to injections.
One study found there was a significant interspecies difference in the drug elimination rate for Noopept.
Extensive and rapid metabolism is observed in rats following intravenous administration with an elimination half-life of 16 minutes. [5] Noopept is eliminated at a slower rate in rabbits and an even slower rate in humans. [6]
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Metabolites
Noopept may be bioactive itself, but much of its neurological effects are attributed to its chief metabolite cycloprolylglycine.
A 5mg/kg injection of Noopept increases Cycloprolylglycine levels in the brain 2.5-fold from a concentration of from 2.8nmol/g to 6.7nmol/g. [8] This is why you will often see Noopept referred to as a cycloprolylglycine pro-drug.
As mentioned previously, Noopept itself has an elimination half-life of 16 minutes in rats and is not detectable in plasma within 25 minutes following oral injestion. [5]
However, the effects of Noopept on brainwave activity have been noted for over 70 minutes following administration. [7]
This suggests that the changes caused by Noopept are primarily the result of increased cycloprolylglycine levels in the brain.
Cycloprolylglycine is observed to have some nootropic effects when injected in rat trials. But the effects of cycloprolylglycine administration do not entirely mimic those of Noopept.
In one trial, 0.5mg/kg injections and 10mg/kg oral ingestion of Noopept resulted in an anti-amnesiac effect that increased over a period of 9 days of consistent dosing.
The same subchronic buildup effect was not observed when administering cycloprolylglycine injections. [9]
Noopept Effects on NGF and BNDF
Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) are proteins integral to the growth, development and maintenance of neurons.
They are implicated in mediating the synaptic plasticity and signalling functions that underlie our abilities to learn and remember. [10]
0.5mg/kg dosages of Noopept administered to rats resulted in an increase in NGF and BDNF in the hippocampus.
Increases were sustained following 28 days of the same dosage with no signs of tolerance developing. [4]
This suggests a potential for long-term improvements to memory capacity with chronic dosing of Noopept.
Memory Enhancing Effects
Noopept is described as possessing “cholinomimetic” properties and a “cholinosensitizing” effect. [15, 4]
Both descriptions point to an increase in cholinergic activity (acetylcholine neurotransmission) as the primary mechanism by which Noopept enhances cognition and memory function.
This mechanism of action is shared by other substances in the Racetam class of nootropics.
In one 56 day human trial, a 20 mg daily dosage of Noopept was more effective than 1200 mg of Piracetam in improving Mini–Mental State Examination (MMSE) scores in persons with cognitive impairments caused by cerebrovascular insufficiency.
Noopept was also effective in improving global MMSE scores in persons with cerebral insufficiency caused by a trauma. Piracetam was not found effective for this group. [3]
NMRI mice that undergo an olfactory bulbectomy begin to develop Alzheimer’s disease-like behaviors that include impairment of spatial memory function and regional neuronal degeneration.
Administering a 0.01 mg/kg dose of Noopept to these mice for a total of 26 days restored spatial memory function.
Noopept also caused an enhanced immune response to elevated levels of Abeta((25-35)) peptide prefibrillar aggregates. [15]
Administration of 0.5mg/kg of Noopept was found to improve memory retention in rats following electroshock therapy to induce amnesia. [9]
In another study, administering Noopept 24 hours following a learning activity was associated with improved memory formation.
Other studies have found that the ideal time to administer Noopept for maximal memory enhancement is 1 hour prior to a learning process. [15]
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Anxiolytic Effects
In a 56 day human trial, 20mg of Noopept per day was administered to patients with cognitive impairments caused by vascular cerebral damage or post-traumatic damage.
In both groups, Noopept was reported to improve symptoms of fatigue, anxiety, irritability, and apathy. In the group diagnosed with vascular cerebral damage, taking Noopept also resulted in improved mood, sleep and daytime wakefulness. [3]
Noopept is observed to increase inhibitory synaptic transmission in the hippocampus. It was found to increase the frequency of Inhibitory Post-Synaptic Currents (IPSCs) in interneurons terminating on the Hippocampal CA1 pyramidal cells.
This mechanism is suggested by Kondratenko et al to mediate the anxiolytic effects of Noopept. [11]
Anti-Depressant Effects
Learned helplessness is an accepted animal model of depression. In this state, animals are made to endure negative or painful stimuli and they become unable or unwilling to take action to avoid the stimuli even if it can be avoided.
Uyanaev et al studied the effects of Noopept on the incidence of the learned helplessness neurosis in rats.
They found that administering Noopept for 21 days eliminated learned helplessness by increasing the percentage of subjects that were trained to avoid the stimuli. [13]
Another study by the same research team found that Noopept dosages of 0.05-0.10 mg/kg resulted in accelerated acquisition of the response required to avoid the negative stimuli. [12]
Neuroprotective Effects
Noopept shows a significantly greater neuroprotective effect than Piracetam or the antioxidant Vitamin E. In a trial, Noopept was tested on two models of degenerated neurons caused by oxidative stress.
The first was on normal human cortical neurons that had been treated with H(2)O(2) and the second on Down’s syndrome cortical neurons.
The normal cortical cultures were treated with 50 microM H(2)O(2) for 1 hour, resulting in degeneration of 60% of the neurons. [14]
Following administration of Noopept, there was a significant increase in the rate of neuronal survival.
Noopept was found to inhibit the build-up of free radicals and peroxidized lipids in neurons treated with H(2)O(2) or FeSO(4). Both of these are markers of oxidative damage.
Chronic treatment with Noopept also enhanced neuronal survival in Down’s syndrome cortical neurons and reduced the appearance of degenerative structural changes.
These results suggest that Noopept possesses significant anti-oxidant properties and neuroprotective effects that could, “present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders.” [14]
Noopept Safety and Side Effects
There is limited scientific data examining the effects of Noopept in humans. In one human study, patients with mild cognitive disorders were administered 10mg of Noopept twice a day for 56 days.
The study found that it was well tolerated with 1.8-fold fewer side-effects reported compared to a group given 1200mg daily dosages of Piracetam. [3]
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- Gudasheva, TA, et al. Synthesis and antiamnesic activity of a series of N-acylprolyl containing dipeptides. European Journal of Medicinal Chemistry. 1996;31(2):151–157
- Ostrovskaia RU, et al. The original novel nootropic and neuroprotective agent noopept. Eksp Klin Farmakol. 2002 Sep-Oct;65(5):66-72.
- Neznamov GG, Teleshova ES. Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin. Neurosci Behav Physiol. 2009 Mar;39(3):311-21. doi: 10.1007/s11055-009-9128-4.
- Ostrovskaya RU, et al. Noopept stimulates the expression of NGF and BDNF in rat hippocampus. Bull Exp Biol Med. 2008 Sep;146(3):334-7.
- Boiko SS, et al. Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration. Bull Exp Biol Med. 2000 Apr;129(4):359-61.
- Boiko SS, et al. Interspecies differences of noopept pharmacokinetics. Eksp Klin Farmakol. 2004 Jan-Feb;67(1):40-3.
- Vorobyov V, et al. Effects of nootropics on the EEG in conscious rats and their modification by glutamatergic inhibitors. Brain Res Bull. 2011 May 30;85(3-4):123-32.
- Gudasheva TA, et al. The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine. Eur J Drug Metab Pharmacokinet. 1997 Jul-Sep;22(3):245-52.
- Ostrovskaya RU, et al. Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration. Bull Exp Biol Med. 2001 Oct;132(4):959-62.
- Tyler WJ, et al. From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem. 2002 Sep-Oct;9(5):224-37.
- Kondratenko RV, Derevyagin VI, Skrebitsky VG. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells. Neurosci Lett. 2010 May 31;476(2):70-3.
- Uyanaev AA, Fisenko VP, Khitrov NK. Effect of noopept and afobazole on the development of neurosis of learned helplessness in rats. Bull Exp Biol Med. 2003 Aug;136(2):162-4.
- Uyanaev AA, Fisenko VP. Studies of long-term noopept and afobazol treatment in rats with learned helplessness neurosis. Bull Exp Biol Med. 2006 Aug;142(2):202-4.
- Pelsman A, et al. GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons. Int J Dev Neurosci. 2003 May;21(3):117-24.
- Ostrovskaya RU, et al. The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model. J Psychopharmacol. 2007 Aug;21(6):611-9.
- Gudasheva TA, et al. Anxiolytic activity of endogenous nootropic dipeptide cycloprolylglycine in elevated plus-maze test. Bull Exp Biol Med. 2001 May;131(5):464-6.
- Jia X, et al. Neuroprotective and nootropic drug noopept rescues ?-synuclein amyloid cytotoxicity. J Mol Biol. 2011 Dec 16;414(5):699-712. doi: 10.1016/j.jmb.2011.09.044. Epub 2011 Oct 1.
- Ostrovskaya RU, et al. Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model. Behav Pharmacol. 1999 Sep;10(5):549-53.
- Radionova KS, Belnik AP, Ostrovskaya RU. Original nootropic drug noopept prevents memory deficit in rats with muscarinic and nicotinic receptor blockade. Bull Exp Biol Med. 2008 Jul;146(1):59-62.
- Bel'nik AP, Ostrovskaya RU, Poletaeva II. Genotype-dependent characteristics of behavior in mice in cognitive tests. The effects of Noopept. Neurosci Behav Physiol. 2009 Jan;39(1):81-6.
- Upchurch M, Wehner JM. Inheritance of spatial learning ability in inbred mice: a classical genetic analysis. Behav Neurosci. 1989 Dec;103(6):1251-8.
- Passino E, et al. Genetic approach to variability of memory systems: analysis of place vs. response learning and fos-related expression in hippocampal and striatal areas of C57BL/6 and DBA/2 mice. Hippocampus. 2002;12(1):63-75.
- Schwegler H, et al. Water-maze learning in the mouse correlates with variation in hippocampal morphology. Behav Genet. 1988 Mar;18(2):153-65.
- Romanova GA, et al. Antiamnesic effect of acyl-prolyl-containing dipeptide (GVS-111) in compression-induced damage to frontal cortex. Bull Exp Biol Med. 2000 Sep;130(9):846-8.
- Andreeva NA, et al. Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress. Bull Exp Biol Med. 2000 Oct;130(10):969-72.
- Zarubina IV, Shabanov PD. Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia. Bull Exp Biol Med. 2009 Mar;147(3):339-44.
- Belnik AP, Ostrovskaya RU, Poletaeva II. Dipeptide preparation Noopept prevents scopolamine-induced deficit of spatial memory in BALB/c mice. Bull Exp Biol Med. 2007 Apr;143(4):431-3.
- Romanova GA, et al. Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept. Bull Exp Biol Med. 2002 Dec;134(6):528-30.
- Romanova GA, et al. Relationship between changes in rat behavior and integral biochemical indexes determined by laser correlation spectroscopy after photothrombosis of the prefrontal cortex. Bull Exp Biol Med. 2004 Feb;137(2):135-8.
- Ostrovskaya RU, et al. The novel substituted acylproline-containing dipeptide, GVS-111, promotes the restoration of learning and memory impaired by bilateral frontal lobectomy in rats. Behav Pharmacol. 1997 Jun;8(2-3):261-8.
- Trofimov SS, Voronina TA, Guzevatykh LS. Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats. Bull Exp Biol Med. 2005 Jun;139(6):683-7.
- Fuxe K, et al. GABA and benzodiazepine receptors. Studies on their localization in the hippocampus and their interaction with central dopamine neurons in the rat brain. Adv Biochem Psychopharmacol. 1981;26:61-76.
- Bertoglio LJ, Joca SR, Guimarães FS. Further evidence that anxiety and memory are regionally dissociated within the hippocampus. Behav Brain Res. 2006 Nov 25;175(1)
- Uversky VN. Alpha-synuclein misfolding and neurodegenerative diseases. Curr Protein Pept Sci. 2008 Oct;9(5):507-40.
- Zamotin V, et al. Cytotoxicity of albebetin oligomers depends on cross-beta-sheet formation. FEBS Lett. 2006 May 1;580(10):2451-7.
- Malisauskas M, et al. Does the cytotoxic effect of transient amyloid oligomers from common equine lysozyme in vitro imply innate amyloid toxicity. J Biol Chem. 2005 Feb 25;280(8):6269-75.
- Xue WF, et al. Fibril fragmentation in amyloid assembly and cytotoxicity: when size matters. Prion. 2010 Jan-Mar;4(1):20-5.
- Ostrovskaya RU, Belnik AP, Storozheva ZI. Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats). Bull Exp Biol Med. 2008 Jul;146(1):77-80.
- Lutsenko VK, Vukolova MN, Gudasheva TA. Cyclopropyl glycine and proline-containing preparation noopept evoke two types of membrane potential responses in synaptoneurosomes. Bull Exp Biol Med. 2003 Jun;135(6):559-62.
- Solntseva EI, et al. The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels. Gen Pharmacol. 1997 Jul;29(1):85-9.
- Bukanova JV, Solntseva EI, Skrebitsky VG. Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons. Int J Neuropsychopharmacol. 2002 Sep;5(3):229-37.
- Kovalenko LP, et al. Immunopharmacological properties of noopept. Bull Exp Biol Med. 2007 Jul;144(1):49-52.
- Prass K, et al. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003 Sep 1;198(5):725-36.
Article last updated on: July 24th, 2018 by Nootriment