Noopept (Russian: Ноопепт; GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) 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. Additional reported effects include:
Formal Name：1-(2-phenylacetyl)-L-prolyl-glycine, ethyl ester
Molecular Weight: 318.367 g/mol
CAS Number: 157115-85-0
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. Noopept was first developed by JSC LEKKO Pharmaceuticals in Russia in 1996 as a prodrug of the endogenous neuropeptide cycloprolylglycine. 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. It has also been found to possesses an anxiolytic effect as well mild psychostimulant-like effects.
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. 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.
Noopept is commonly prescribed as a general nootropic in many countries. Most people can obtain it easily by prescription in order to improve cognitive function. Noopept has been shown to be very safe with limited tolerance and withdrawal problems. Some doctors also prescribe it to aid in the reduction of symptoms in patients with neurological diseases. Noopept is often used alone or in conjunction with other therapies.
At the moment, Noopept is not regulated in North America and other countries. A US patent exists for the drug however it has not been registered for approval to be marketed as a prescription. Noopept is quite strong vs. the racetam family and needs to be used with caution. If used at the recommended dosages, side effects should be limited one should be able to greatly improve cognitive performance.
1000 x Piracetam
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.
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. 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.
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.
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. 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. 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.
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.
Administration of 0.5mg/kg of Noopept was found to improve memory retention in rats following electroshock therapy to induce amnesia. 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.
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.
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.
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. 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.
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.
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.”
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.
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