New endogenous dipeptide cycloprolyl-glycine is similar to piracetam by its mnemotropic selectivity

Gudasheva, T. A.; Ostrovskaya, R. U.; Трофимов, С. С.; Воронина, Т. А.; Сколдинов, А. П.; Seredenin, S. B.

doi:10.1007/bf02433192

Cited by 16 publications

(3 citation statements)

References 7 publications

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“…The in vivo investigations of cyclo (Pro—Gly) showed that this dipeptide has pharmacological profile resemble that of Piracetam. Like Piracetam, cyclo (Pro—Gly) possess nootropic [22], neuroprotective, antihypoxic [23] and anxiolytic [24] activities. Evaluation of the effect on memory phases in passive avoidance test in rats demonstrated that cyclo (Pro—Gly) similar to Piracetam is active only when administered before learning.…”

Section: Noopept a Dipeptide Nootropic Drugmentioning

confidence: 99%

Novel Technologies for Dipeptide Drugs Design and their Implantation

Gudasheva

Ostrovskaya

Середенин

2018

CPD

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The article is an overview of author’s data obtained in the framework of the project “The Creation of dipeptide preparations” at the V.V. Zakusov Institute of Pharmacology, Moscow, Russia. Advantages of dipeptides over longer peptides consist in that they are orally active owing to higher sta-bility and ability to penetrate biological barriers due to the presence of specific ATP–dependent trans-porters in enterocytes and blood-brain barrier. Two original approaches for dipeptide drugs design have been developed. Both of them are based on the idea of a leading role of central dipeptide fragment of the peptide chain beta-turn in the peptide-receptor interaction. The first approach, named “peptide drug-based design” represents the transformation of known nonpeptide drug into its dipeptide topological analog. The latter usually corresponds to a beta-turn of some regulatory peptide. The second approach represents the design of tripeptoide mimetic of the beta-turn of regulatory peptide or protein. The results of the studies, which led to the discovery of endogenous prototypes of the known non-peptide drugs piracetam and sulpiride, are presented herein. The paper discusses the process, based on the above-mentioned principles, that was used in designing of nontoxic, orally available, highly effective dipeptide drugs: nootropic noopept, dipeptide analog of piracetam; antipsychotic dilept, neurotensin tripeptoid analog; selective anxiolytic GB-115, tripeptoid analog of CCK-4, and potential neuroprotector GK-2, homodimeric dipeptide analog of NGF.

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Section: Noopept a Dipeptide Nootropic Drugmentioning

confidence: 99%

Novel Technologies for Dipeptide Drugs Design and their Implantation

Gudasheva

Ostrovskaya

Середенин

2018

CPD

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“…Since CPG synthesis in 1991 and its discovery as an endogenous compound in rat brain in 1996 (Gudasheva et al, 1996a), in vitro and animal studies have revealed a wide range of CPG psychotropic activities. It was shown that the dipeptide possesses antiamnesic (Gudasheva et al, 1999), anxiolytic (Seredenin et al, 2002), antihypoxic, and neuroprotective effects (Povarnina et al, 2016). Previously it was shown that CPG chronic administration significantly decreased immobility time in inbred BALB/c mice in the forced swim test (FST) (1 and 2 mg/kg, 2 weeks, i.p.)…”

Section: Introductionmentioning

confidence: 99%

The neuropeptide cycloprolylglycine produces antidepressant-like effect and enhances BDNF gene expression in the mice cortex

et al. 2022

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Background: Cycloprolylglycine (CPG) is an endogenous dipeptide with a wide range of psychotropic activity and putative therapeutic potential for depression. A small but growing body of data suggests that antidepressant-like effect of CPG is associated with neuroplastic changes in the brain or 5-HT system modulation. However, the mechanisms of the dipeptide action remain elusive. Aims: Here, we characterize the effects of chronic CPG administration on behavior and genes expression of antidepressants sensitive catalepsy (ASC) mice strain, characterized by depressive-like behavior. Methods: ASC mice were injected with saline, fluoxetine (10 mg/kg/day), or CPG (1 and 2 mg/kg/day) during 2 weeks. Behavior was studied using the open field test, novel object test, elevated plus maze test, forced swim test, and tail suspension test (TST). The expressions of genes coding BDNF, CREB, 5-HT1A and 5-HT2A receptors, TPH2, and SERT in the brain were measured with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: Chronic intraperitoneal administration of 1 and 2 mg/kg of CPG revealed the significant antidepressant-like effect by decreasing immobility time in the TST. At the same time, CPG did not negatively affect locomotor activity, cognition, or anxiety. In the real-time quantitative polymerase chain reaction (PCR) assay, chronic CPG treatment (2 mg/kg for 14 days) increased Bdnf mRNA level in the frontal cortex. Conclusions: Our findings extend the evidence for the effectiveness of CPG to reduce depressive-like behaviors. The antidepressant-like effect of CPG is mediated, as least in part, by BDNF-dependent mechanism. The exact mechanism remains to be elucidated, and further studies are warranted.

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“…Cyclo-L-prolylglycine (CPG) was designed as a potential peptide prototype of piracetam, the classic nootropic drug [1] and was subsequently discovered as endogenous compound in the brain of intact rats in micromolar concentration [2]. CPG is similar to piracetam both in structure and main pharmacological effects; it possesses nootropic [3], anxiolytic [4,5], antihypoxic [6], neuroprotective [6,7], analgesic [8], and antidepressant [9,10] activities at central administration at doses 100-1000 times smaller than those for piracetam. Recently, we have demonstrated CPG to be ampakine, i.e., a positive modulator of AMPA receptors [11].…”

Section: Introductionmentioning

confidence: 99%

Glyproline Pro-Ampakine with Neuroprotective Activity

Колясникова¹,

Povarnina²,

Таллерова³

et al. 2020

Neuroprotection - New Approaches and Prospects

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Previously it was shown that neuropeptide cyclo-L-prolylglycine (CPG) is a positive modulator of AMPA receptors, which increases BDNF level in neuronal cell cultures. The spectrum of CPG's pharmacological effects corresponds to that of BDNF. Dipeptide N-phenylacetyl-glycyl-L-proline ethyl ester (GZK-111) was designed and synthesized as a linear analog of CPG. The aim of the present work was to reveal the pharmacological profile of GZK-111. Dipeptide GZK-111 was shown to metabolize into CPG in vitro and increased cell survival by 28% at concentrations of 10-7-10-6 M in a Parkinson's disease cell model. In a model of cerebral ischemia, GZK-111, at a dose of 0.5 mg/kg, i.p., was found to have neuroprotective effects, reducing the cerebral infarct volume by 1.6 times. Similar to CPG, GZK-111, at the range 0.1-1.0 mg/kg, i.p., possessed a stereospecific antiamnesic activity. A significant anxiolytic effect was observed at a dose of 1.5 mg/kg. GZK-111, at the range 0.5-4.0 mg/kg, i.p., demonstrated analgesic activity. GZK-111, at a dose of 10 mg/kg/7 days, i.p., possessed antidepressant-like activity. So, the neuroprotective, nootropic, antihypoxic, anxiolytic, antidepressant-like, and analgesic effects of GZK-111 were revealed. Thus, GZK-111 can be considered as a pharmacologically active pro-ampakine with a BDNF-ergic mechanism of action.

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New endogenous dipeptide cycloprolyl-glycine is similar to piracetam by its mnemotropic selectivity

Cited by 16 publications

References 7 publications

Novel Technologies for Dipeptide Drugs Design and their Implantation

Novel Technologies for Dipeptide Drugs Design and their Implantation

The neuropeptide cycloprolylglycine produces antidepressant-like effect and enhances BDNF gene expression in the mice cortex

Glyproline Pro-Ampakine with Neuroprotective Activity

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