Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides

Gudasheva, T. A.; Воронина, Т. А.; Ostrovskaya, R. U.; Rozantsev, G. G.; Vasilevich, N. I.; Trofimov, S. S.; Kravchenko, EV; Сколдинов, А. П.; Seredenin, S. B.

doi:10.1016/0223-5234(96)80448-x

Cited by 61 publications

(27 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Proceeding from the original concept on the peptidergic nature of the nootropic effects of piracetam [4], GVS-111 dipeptide (N-phenylacetyl-L-prolylglycine ethyl ester) was synthesized and pharmacologically tested .in the Institute of Pharmacology, Russian Academy of Medical Sciences [7,9]. The mnemotropic activity of GWS-111 2-4 thousand times surpassed that of piracetam.…”

mentioning

confidence: 97%

NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats

1999

View full text Add to dashboard Cite

The effects of new nootropic dipeptide GVS-111 (N-phenylacetyl-L-prolylglycine ethyl ester) on EEG spectral characteristics were compared with those of piracetam. The EEG was recorded in the cortex and hippocampus of nonanesthetized nonrestrained rats with chronically implanted electrodes. GVS-111 and piracetam induced similar changes in EEG spectral profile in both structures increasing the o~-band power and decreasing the power of the 13-and 6-bands. These effects were prevented by intracerebral injection of 10 -~~ mol NMDA receptor antagonist (• acid. The data correlate with behavioral and neurochemical findings and suggest that NMDA receptors can be specifically involved in the mechanisms of nootropic effects of piracetam and GVS-111. In this study we compared the effects of GVS-111 and piracetam on spectral characteristics of EEG in the cortex and hippocampus of free-moving rats and assessed the involvement of NMDA receptors in these effects. The choice of these two structures was determined by the data on cortical and subcortical effects of nootropic drugs [2]. MATERIALS AND METHODSExperiments were carried out on 8 conscious fleemoving male Wistar rats weighing 350-420 g. Nichrome electrodes (0.4 mm in diameter) were implanted in the symmetrical areas of the somatosensory cortex and dorsal hippocampus (CA 1 area) of the right hemisphere under Nembutal anesthesia (50 mg/kg, subcutaneously). A cannula was implanted in the right lateral ventricle using a modified Meshcherski stereotaxic apparatus according to the rat brain atlas coordinates [11] AP=-0.4, L=3.2, H=3.7, ~=20, where o~ is the angle between the sagittal plane and the cannula.

show abstract

mentioning

confidence: 97%

NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats

1999

View full text Add to dashboard Cite

show abstract

“…An original concept of creation of psychotropic agents was developed during several years at Institute of Pharmacology by T. A. Gudasheva: dipeptides simulating the structure of non-peptide neurotropic preparations and peptide active center with predominating activity of the corresponding type are created [9]. Comparison of the structure of standard nootrope (piracetam) with the structure of N-terminal fragment of the main fragment of vasopressin ("memory peptide") led to creation of a series of acylproline-containing dipeptides [14], from which N-phenylacetyl-L-prolylglycine ethyl ether (GVC-111; Noopept) was selected.…”

mentioning

confidence: 99%

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by β-amyloid25–35 injection into Meynert basal nuclei of rats)

2008

View full text Add to dashboard Cite

Experiments on adult Wistar rats showed that injection of beta-amyloid25-35 (2 microg) into Meynert basal nuclei caused long-term memory deficiency which was detected 24 days after this injection by the memory trace retrieval in conditioned passive avoidance reflex (CPAR). The effects of noopept, an original nootropic and neuroprotective dipeptide, on the severity of this cognitive deficiency were studied. Preventive (for 7 days before the injury) intraperitoneal injections of noopept in a dose of 0.5 mg/kg completely prevented mnestic disorders under conditions of this model. Noopept exhibited a significant normalizing effect, if the treatment was started 15 days after the injury, when neurodegenerative changes in the basal nuclei, cortex, and hippocampus were still acutely pronounced. The mechanisms of this effect of the drug are studied, including, in addition to the choline-positive effect, its multicomponent neuroprotective effect and stimulation of production of antibodies to beta-amyloid25-35. Noopept efficiency in many models of Alzheimer disease, its high bioavailability and low toxicity suggest this dipeptide for further studies as a potential agent for the treatment of this condition (initial and moderate phases).

show abstract

“…A new method developed at the Institute of Pharmacology suggests the synthesis of dipeptide drugs, which imitate the structure of a nonpeptide substance and active site of the peptide with neurotropic properties. N-acyl proline derivatives with nootropic activity were synthesized from the active fragment of the major vasopressin metabolite AVP [4][5][6][7][8][9] and nonpeptide prototype of piracetam [8]. Among these preparations, N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111, Noopept) is characterized by high activity, low toxicity, and peroral bioavailability.…”

mentioning

confidence: 99%

Noopept stimulates the expression of NGF and BDNF in rat hippocampus

et al. 2008

View full text Add to dashboard Cite

We studied the effect of original dipeptide preparation Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) with nootropic and neuroprotective properties on the expression of mRNA for neurotropic factors NGF and BDNF in rat hippocampus. Expression of NGF and BDNF mRNA in the cerebral cortex and hippocampus was studied by Northern blot analysis. Taking into account the fact that pharmacological activity of Noopept is realized after both acute and chronic treatment, we studied the effect of single and long-term treatment (28 days) with this drug. Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect. These changes probably play a role in neuronal restoration. We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment. Moreover, therapeutic effectiveness of Noopept should be evaluated at the initial stage of Alzheimer's disease.

show abstract

Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides

Cited by 61 publications

References 13 publications

NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats

NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by β-amyloid25–35 injection into Meynert basal nuclei of rats)

Noopept stimulates the expression of NGF and BDNF in rat hippocampus

Contact Info

Product

Resources

About