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GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester, , (CAS Number) 157115-85-0, (PubChem) CID 180496, C17H22N2O4

Among the studies cited, the effective doses ranged from .01mg/kg to 10 mg/kg (in rats and mice); when subjected to allometric scaling, this range would be equivalent to .002mg/kg to 2.445 mg/kg in humans [7,10,13]. In a 70kg (154lbs) adult human, the dosing range would be 171mcg to 171mg.

Typically, the most cited dosing range (anecdotally) is 10-30mg, up to 3 times per day, usually dosed sublingually or orally.

Patented in 1995, Noopept is a Nootropic substance that is a dipeptide similar in effect to Piracetam [3]; it is often cited as being 1000 times more potent (by weight) than Piracetam. Noopept has high oral bioavailability, and appears to potentiate its own effects with chronic administration. Noopept has shown promise in treating many different aspects of cognitive decline that warrants more research, especially in human models.

Noopept has been noted to have four main mechanisms of action; the first noted mechanism of action is antioxidation: in vitro studies of Noopept have shown signs that it operates on an antioxidative mechanism of action which protects neurons from apoptosis [4]. The second noted mechanism of action of Noopept is inhibition of glutamate neurotoxicity [1]; glutamate neurotoxicity leads to quick cell death, and is linked to a variety of neurological disorders such as autism and Alzheimers disease. The third mechanism of action of Noopept is increased neuronal plasticity [7], which can lead to greater adaptability in learning and memory. The fourth mechanism of action that has been noted in Noopept is increases expression of phenylacetic acid, prolyglycine, and cyclo-prolyglycine in the brain [12], which are endogenous Nootropics.

What makes Noopept an intriguing nootropic is its myriad of positive effects, lack of noted negative side effects, and its effectiveness in both chronic and acute usage. In both in vivo and in vitro models, Noopept was shown to have positive effects on all stages of memory, from learning to recall, as well as anxiolytic effects [1]. An in vitro study showed Noopept to be neuroprotective against the use of H2O2 in neuronal degradation, in both healthy brains as well as those with Downs Syndrome in a dose-dependent manner [4]. In rat models of memory impairment, Noopept was shown to improve memory retention and retrieval, and improve learning which was shown through the use of passive avoidance response testing [6]. Rats with ischemic lesions were treated with Noopept for nine days and then tested with the passive avoidance test; those rats that had been treated performed significantly better than the control group; Noopept was also shown to be neuroprotective through antioxidation in the rats who received treatment for nine days [7]. Studies also showed that rats given a single oral administration of Noopept showed improved scores on the passive avoidance test [10]. Another study showed that rats who had gone through olfactory bulbectomies showed Alzheimers like symptoms, but after 21 days of dosing Noopept, spatial memory improved greatly which was evidenced through the use of the Morris Water Maze test [13].

Two other interesting benefits of Noopept were noted; one dealing with BDNF and NGF, and the other dealing with the immune system. One study showed rats treated with Noopept, both chronically and acutely, were found to have a higher expression of mRNA BDNF and NGF; even more interestingly, after 28 days of treatment no tolerance towards Noopept was detected and there was some evidence the effects of Noopept potentiate the longer it is administered [8]. Another study looked at the effect of Noopept on immune deficient mice; the researchers found Noopept to have immuno-corrective properties [5].

Among the studies cited, doses up to 10mg/kg in rats have shown no toxicity, which when subjected to allometric scaling yields a dose of 2.445mg/kg in humans (or 171 mg for a 70kg person); in fact, Noopept has been shown to be neuroprotective at said dosage [7,10,13].

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European Union and United Kingdom: Intellimeds ( Powder|Capsules|10mg Tablets|20mg Tablets)

Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB. The original novel nootropic and neuroprotective agent noopept. Eksp Klin Farmakol. 2002 Sep-Oct;65(5):66-72. [1]

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. Neuroscience and Behavioral Physiology Volume 39, Issue 3 , pp 311-321. [2]

SEREDENIN SERGEI B, VORONINA TATIANA A, GUDASHEVA TATIANA A, OSTROVSKAYA RITA U,

ROZANTSEV GRIGORI G, SKOLDINOV ALEXANDER P, TROPHIMOV SERGEI S, HALIKAS JAMES A, GARIBOVA TAISIJA L. Biologically active n-acylprolydipeptides having antiamnestic, antihypoxic and anorexigenic effects. US5439930 (A) 1995-08-08. [3]

Alejandra P, Hoyo-Vadillo C, Gudasheva T, Serednin S, Ostrovskaya R, Busciglio J. GVS-111 prevents oxidative damage and apoptosis in normal and Downs Syndrome human cortical neurons. International Journal of Developmental Neuroscience, Vol 21 Issue 3 May 2003 Pages 117-124. [4]

Kovalenko, Shipaeva, Alekseeva, Pronin, Durnev, Gudasheva, Ostrovskaja, Seredenin. Immunopharmacological properties of noopept. Bulletin of Experimental Biology and Medicine Volume 144, Issue 1 , pp 49-52. [5]

G. A. Romanova, F. M. Shakova, T. A. Gudasheva, R. U. Ostrovskaya. Impairment of Learning and Memory after Photothrombosis of the Prefrontal Cortex in Rat Brain: Effects of Noopept. Bulletin of Experimental Biology and Medicine Volume 134, Issue 6 , pp 528-530. [6]

Ostrovskaya R, Romanova G, Barskov I, Shanina E, Gudasheva T, Victorov I, Voronina T, Seredenin S. Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model. Behavioural Pharmacology: September 1999. [7]

R. U. Ostrovskaya, T. A. Gudasheva, A. P. Zaplina, Ju. V. Vahitova, M. H. Salimgareeva, R. S. Jamidanov, S. B. Seredenin. Noopept stimulates the expression of NGF and BDNF in rat hippocampus. Bulletin of Experimental Biology and Medicine Volume 146, Issue 3 , pp 334-337. [8]

S. S. Boiko, R. U. Ostrovskaya, V. P. Zherdev, S. A. Korotkov, T. A. Gudasheva, T. A. Voronina, S. B. Seredenin. Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration. Bulletin of Experimental Biology and Medicine Volume 129, Issue 4 , pp 359-361. [9]

R. U. Ostrovskaya, T. Kh. Mirsoev, G. A. Romanova, T. A. Gudasheva, E. V. Kravchenko, C. C. Trofimov, T. A. Voronina, S. B. Seredenin. Proline-Containing Dipeptide GVS-111 Retains Nootropic Activity after Oral Administration. Bulletin of Experimental Biology and Medicine Volume 132, Issue 4 , pp 959-962. [10]

Solntseva E, Bukanova J, Ostrovskaya R, Gudasheva T, Voronina T, Skrebitsky V. The effects of piracetam and its novel dipeptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels. General Pharmacology: The Vascular System, Volume 29 Issue 1, July 1997. [11]

T. A. Gudasheva, S. S. Boyko, R. U. Ostrovskaya, T. A. Voronina, V. K. Akparov, S. S. Trofimov, G. G. Rozantsev, A. P. Skoldinov, V. P. Zherdev, S. B. Seredenin. The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclol-prolylglycine. European Journal of Drug Metabolism and Pharmacokinetics Volume 22, Issue 3 , pp 245-252. [12]

Ostrovskaya RU, Gruden MA, Bobkova NA, Sewell RD, Gudasheva TA, Samokhin AN, Seredinin SB, Noppe W, Sherstnev VV, Morozova-Roche LA. The nootropic and neuroprotective prolinecontaining dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimers disease model. J Psychopharmacol August 2007 vol. 21 no. 6 611-61

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