Noopept

A synthetic proline-containing dipeptide (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) studied as a cognition enhancer, with a mechanism centred on neurotrophin expression and HIF-1 activation.

What it is

Noopept is a small synthetic dipeptide, N-phenylacetyl-L-prolylglycine ethyl ester, developed at the V. V. Zakusov Institute of Pharmacology in Moscow and originally designated GVS-111. It was designed as a peptide analogue of the classic racetam nootropics, engineered so that a proline residue mimics the pyrrolidinone ring of piracetam while the phenylacetyl and glycine ethyl ester groups improve metabolic stability and membrane penetration. Despite its "peptide" description it is a compact two-residue molecule rather than a long chain, which is why it is studied at doses roughly 1000-fold lower than piracetam.

By research class Noopept is a proline-containing dipeptide cognition enhancer with reported neuroprotective activity. It sits alongside the Russian neuro-active peptides Semax and Selank in the same broad research programme, though its chemistry and mechanism are distinct. Supplied strictly for laboratory research use only, not for human or veterinary use.

How it works

The most striking molecular finding is that Noopept increases the DNA-binding activity of hypoxia-inducible factor 1 (HIF-1). At 10 uM in cell culture it raised basal HIF-1 DNA-binding activity by roughly 43%, while leaving eight other transcription factors (including CREB, NF-kB, p53 and STAT1) unchanged. The proposed upstream target is inhibition of prolyl hydroxylase 2 (PHD2), which stabilises the oxygen-sensitive HIF-1 alpha subunit; molecular docking indicated that the active L-isomer binds the PHD2 active site while the inactive D-form does not. HIF-1 stabilisation in turn drives a broad protective gene programme spanning angiogenesis, glucose transport, antioxidant enzymes and neurotrophic factors.

A second, well-replicated line of work shows that Noopept raises the expression of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the rat hippocampus. Acute dosing increased hippocampal mRNA for both neurotrophins, and 28-day chronic treatment did not produce tolerance but instead sustained and even potentiated the BDNF effect. Downstream, Noopept has been reported to reduce the activity of stress-activated kinases (SAPK/JNK and pERK1/2), to show choline-positive (cholinergic) properties, and to attenuate amyloid-beta toxicity, tau hyperphosphorylation and oxidative stress in cellular models. Together these effects are interpreted as promoting synaptic plasticity and memory consolidation.

What the research shows

The headline human data come from a 56-day comparative clinical study by Neznamov and Teleshova (2009) in patients with mild cognitive disorders of vascular or post-traumatic origin. Noopept at 10 mg twice daily (20 mg/day) was compared with piracetam at 400 mg three times daily (1200 mg/day). The Noopept group improved on most cognitive and mood measures, with Mini-Mental State Examination (MMSE) scores rising from 26 to 29, an earlier onset of effect and fewer adverse events, all at a dose roughly 120-fold lower than the piracetam comparator. Mechanistic support comes from Ostrovskaya's neurotrophin work and from a 2014 Alzheimer's cellular model showing marked reductions in apoptosis and restoration of cell viability.

Safety signals in the literature

In the Neznamov and Teleshova comparative trial the adverse events reported in the Noopept arm (31 patients) were sleep disturbance in 5 of 31, irritability in 3 of 31 and increased blood pressure in 7 of 31, with the overall tolerability described as favourable relative to piracetam. These are third-party clinical observations in a research population and are recorded here only to characterise the compound; they are not use guidance. Supplied strictly for laboratory research use only, not for human or veterinary use.

At a glance

Preparing it

When supplied as a lyophilised powder, Noopept is reconstituted before laboratory use. See the reconstitution guide for adding bacteriostatic or sterile diluent to the vial without foaming the solute, and the concentration guide for calculating the amount of compound per unit volume once dissolved. Store reconstituted material cold, typically 2-8 C, and protect the powder from moisture and light before use.

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