Cycloprolylglycine structure

Cycloprolylglycine is known as one of the Noopept metabolites. Researches of Noopept mechanism of action suggest that this neuropeptide responsible for its Nootropic effects. In this article, I will share some highlights of the studies of this compound.

The cyclic dipeptide Cyclo-L-prolylglycine was first discovered in 1991 as peptide prototype of Piracetam. Later in 1996, it was found as an endogenous compound in rat brain at micromolar concentrations. Its pharmacological effects are somewhat similar to Piracetam. It selectively modulates memory and learning processes, and show anxiolytic, anti-hypoxic and anti-amnesic effects.

Effects of Cycloprolylglycine on BDNF

A new study performed in 2016 found that Cycloprolylglycine, as well as Piracetam, can increase BDNF levels in Neuronal cells. The experiment was conducted on cultures of mouse hippocampal cells and human neuroblastoma cells using the models of glutamate and 6-OHDA toxicity.

In the neuroblastoma cells of human, 10^-3M of Piracetam and CPG increased BDNF content by 30%. CPG at the concentration of 10^-7 M showed 64% increase of Brain-Derived Neurotrophic Factor compared to control.


cycloprolylglycine bdnf

The similar results were obtained in cells affected by damaging conditions. Both Piracetam and Cycloprolylglycine increased BDNF content, but CPG was effective at 10.000 times lower concentrations.

CycloprolylGlycine as a positive AMPA modulator

It is known that Piracetam and some other Racetams acts as a positive modulator of the AMPA receptors. Positive modulation of the AMPA receptors also stimulates the release of BDNF. In a previous study, it was found that Piracetam and Cycloprolylglycine increase BDNF in neuronal cells. This suggests that CPG may be a positive allosteric AMPA modulator. The next study is dedicated to the impact of this neuropeptide on the current of AMPA receptors.

This experiment was performed on rat Purkinje cells using the patch-clamp technique. As AMPA receptors stimulator, researchers used Kainate solution. The results show that Cycloprolylglycine potentiates AMPA receptors currents by up to 55% compared to control.

effect on ampa receptors

Older studies of the CPG and its analogs revealed the anxiolytic action of this peptide. The results of the Elevated Plus-Maze Test on rats showed that 0.05mg/kg injection of the Cycloprolylglycine significantly increases the time spent in open arms compared to the control.


This information could be taken with a grain of salt. As you can see, this compound mostly studied by the same people. Some of them working in Zakusov Institute of Pharmacology, where Noopept was created. However, the institute is on state property and budget-funded, they are also don’t mention Noopept in those researches. Zakusov Institute working on new peptide anxiolytic, nootropic, and antidepressant drugs right now. The development of the new drugs already funded and in the stage of pre-clinical trials. So it is logical to assume that they are studying various substances like CPG and its analogs to discover new nootropics rather than to provide scientific support to the existing ones. But that’s only my opinion.




  1. Gudasheva T.A, Koliasnikova K.N, Antipova T.A, Seredenin S. B. “Neuropeptide Cycloprolylglycine Increases the Levels of Brain-Derived Neurotrophic Factor in Neuronal Cells.”
  2. Grigoriev V.V, Kolyasnikova K.N, Gudasheva T.A, Zamoysky V.L, Seredinin S.B “Neuropeptide Cycloprolylglycine are an endogenous positive modulator of AMPA receptors.”
  3. Gudasheva T.A, Konstantinopolskii M.A, Ostrovskaya R.U, Seredenin S.B “Anxiolytic Activity of Endogenous Nootropic Dipeptide Cycloprolylglycine in Elevated Plus-Maze Test.”