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Cycloprolylglycine is a small cyclic dipeptide found naturally in brain tissue, and the compound usually named as Noopept's active metabolite. It is studied under two names that describe the same molecule: Russian work calls it cycloprolylglycine, New Zealand work calls it cyclic glycine-proline. ⚠️ The active-metabolite claim is weaker than its popularity suggests. The primary source found the compound in untreated animals as well as treated ones, and reported a 2.5-fold rise at a single hour-long timepoint. The same institute later published that Noopept and this metabolite behave differently in a learning task, which is difficult to reconcile with a simple prodrug relationship.
- Genuinely present in brain tissue rather than a synthetic novelty
- Crosses into the cerebrospinal fluid compartment in humans, shown indirectly
- A plausible mechanism sketch linking AMPA activity to BDNF, if any of it holds up
- No toxicology, no repeat-dose study and no human safety data of any kind
- Anticoagulant, clot-dissolving and antiplatelet activity in animals, entirely unfollowed up
- Effects vary by mouse strain, which is a warning about how far any of it generalises
Mechanism
Two separate mechanistic accounts exist for this molecule and they do not overlap.
The Russian account describes it as an endogenous positive modulator of receptors, which raises and produces , anxiolytic and antidepressant effects. The AMPA claim rests on one experiment where 1 micromolar enhanced currents in cerebellar Purkinje cells [1]. ⚠️ There is one concentration, no concentration-response curve, no fitted potency and no binding site.
⚠️ The most careful measurement in the whole literature undercuts that reading. Brief application of 0.1 to 10 micromolar had no effect on -A currents at all; only prolonged application of 1 micromolar raised the current, to 177 percent of control, with slow onset and slow washout [2]. The authors interpret that time course as second messengers, which is to say the compound is doing something upstream rather than sitting on the receptor.
The claim comes from a cell-culture study reporting activity at 0.1 micromolar and at 1 millimolar [3]. ⚠️ Two active concentrations six orders of magnitude apart with nothing between them is not a dose-response.
The New Zealand account is different: the same molecule is described as an derived that competes at IGFBP-3 and so changes how much IGF-1 is available. ⚠️ Note what that mechanism would and would not do. Competing at a binding protein redistributes IGF-1; it does not create more of it.
⚠️ And the molecule is not specific to Noopept. It is a metabolic endpoint for several proline and glycine containing compounds, and is also a common bacterial, fungal and marine natural product, so finding it in a sample says little about where it came from.
receptor fingerprint
receptorsClaimed positive modulator
-A receptorsSlow indirect potentiation
expressionIncreases (downstream)
IGFBP-3 / availabilityProposed competitor
Evidencehow good the literature is
Almost everything comes from one Russian institute, in rodents, at single concentrations.
The metabolite claim traces to a 1997 paper [4]. Read directly, it reports that Noopept itself was undetectable in rat brain an hour after dosing, that three candidate metabolites were present in treated and untreated animals alike, and that only this one rose, by 2.5 times, at that single timepoint. The authors' own conclusion is hedged.
⚠️ The same institute then published a direct complication: in an active-avoidance task Noopept worked after a single oral dose in a way that, in the paper's own words, distinguishes it from this metabolite [5]. A parent and its active metabolite that dissociate behaviourally are not in a simple prodrug relationship.
The human data amounts to one observational study, and it is not a study of this compound. Eleven men with Parkinson's disease took blackcurrant extract for 28 days, and their cerebrospinal fluid levels of the molecule rose [9]. That establishes it reaches the brain compartment; it says nothing about giving it as a drug. Other human findings are correlations in observational cohorts, several from investigators with a commercial interest in the compound.
⚠️ No trial of this compound has ever been registered anywhere.
Dosingtypical ranges, not medical advice
interested in protocols and clinical dosages? make an account to see them! ^_^
Safetyrisks and cautions, not medical advice
No formal toxicology exists, no repeat-dose study has been done, and there is no human safety data.
Rodent doses have been low and no adverse effects are reported, but nothing has been designed to look for them.
⚠️ One signal deserves attention rather than dismissal. Both Noopept and this metabolite have measurable anticoagulant, clot-dissolving and antiplatelet activity in animals and in vitro, with the metabolite active at extremely low concentrations [6]. Nobody has followed that up, and an interaction with blood thinning is a plausible and entirely unexamined risk.
⚠️ Effects also depend on mouse strain. Anxiolytic activity appeared in one strain and not another [7], which is a caution about how well any of this generalises.
History
The molecule was identified in the 1990s at the Zakusov Institute in Moscow during work on Noopept, a dipeptide built as a piracetam analogue, and was proposed as its active metabolite. That framing followed the compound into the supplement world, where it is now sold on the strength of it.
Separately and later, a group in Auckland arrived at the same molecule from a completely different direction, as a metabolite of an IGF-1 fragment, and built a body of biomarker work around the ratio between it and IGF-1. The two literatures rarely cite each other and describe the compound in incompatible terms.
Resources
This entry is here for reference.
Research
- 1997first citedThe major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to…
- 2019most recentEffect of Endogenous Neuropeptide Cycloprolylglycine on GABA(A) Receptors in Cerebellar Purkinj…
- 1.Neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors
- 2.Effect of Endogenous Neuropeptide Cycloprolylglycine on GABA(A) Receptors in Cerebellar Purkinje Cells
- 3.Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells.
- 4.The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine
- 5.Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration
- 6.[Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine].
- 7.Endogenous dipeptide cycloprolylglycine shows selective anxiolytic activity in animals with manifest fear reaction
- 8.Regional and subcellular localization of cycloprolylglycine in rat brain
- 9.Supplementation of Blackcurrant Anthocyanins Increased Cyclic Glycine-Proline in the Cerebrospinal Fluid of Parkinson Patients: Potential Treatment to Improve Insulin-Like Growth Factor-1 Function.
9 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is this really Noopept's active metabolite?
The claim is weaker than its reputation. The original study found Noopept undetectable in rat brain an hour after dosing and found this molecule in untreated animals as well as treated ones, rising 2.5-fold at one timepoint. The same institute later reported the two behave differently in a learning task, which does not fit a straightforward prodrug relationship. It is also a metabolic endpoint for several other compounds and a common natural product in bacteria and fungi.
Are cycloprolylglycine and cyclic glycine-proline different things?
No, they are the same molecule with the same registry number. Two research groups arrived at it from different directions, one through Noopept and one through IGF-1 metabolism, and each kept its own name. Their explanations of what it does have almost nothing in common.
Is there any human evidence?
Almost none, and none of it tests the compound as a drug. The one interventional study gave eleven men with Parkinson's disease blackcurrant extract and measured this molecule going up in their spinal fluid. Everything else is correlation in observational cohorts, some of it from researchers with a commercial stake.
Limitations of the evidence
- Measured hippocampal levels are about a hundred times the concentration at which it is said to become active, and nobody addresses this
- The AMPA claim is one experiment at one concentration with no potency and no binding site
- The cleanest measurement, on GABA-A currents, points to an indirect action rather than receptor binding
- The BDNF result uses two concentrations six orders of magnitude apart
- The active-metabolite claim rests on a 2.5-fold rise at a single timepoint, in a study finding it in controls too
- The same institute reported that Noopept and this metabolite behave differently in a learning task
- No Ki, Kd, IC50 or EC50 at any target, and no trial has ever been registered
Adverse effects
- No toxicology, no repeat-dose study and no human safety data of any kind
- Anticoagulant, clot-dissolving and antiplatelet activity in animals, entirely unfollowed up
- Effects vary by mouse strain, which is a warning about how far any of it generalises