Nootropic

PE-22-28 is a synthetic heptapeptide derived from the propeptide domain of sortilin (specifically residues 22-28), designed as an optimized analogue of spadin, a natural TREK-1 potassium channel blocker. It was developed by researchers at the Institut de Pharmacologie Moléculaire et Cellulaire (IPMC) in France as part of a program to create novel, fast-acting antidepressant candidates that bypass the slow onset of action characteristic of SSRIs and other monoamine-based antidepressants. PE-22-28 represents a conceptually distinct approach to treating depression. Rather than modulating serotonin, norepinephrine, or dopamine reuptake, it targets TREK-1 (TWIK-related potassium channel 1), a two-pore domain potassium channel that regulates neuronal excitability in mood-related brain circuits. TREK-1 knockout mice are naturally resistant to depression-like behaviors, and pharmacological blockade of TREK-1 produces antidepressant effects within days rather than weeks in rodent models.

Pinealon (Glu-Asp-Arg, or EDR) is a synthetic tripeptide developed by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. It is classified as a brain-specific bioregulator peptide, designed to target neuronal tissue and modulate gene expression related to neuroprotection, cognitive function, and circadian rhythm regulation. The name derives from its proposed tropism for pineal and cerebral tissue, though its effects are not limited to the pineal gland. Like other Khavinson bioregulator peptides (Epitalon, Cartalax), Pinealon belongs to the class of ultra-short peptides hypothesized to interact directly with DNA to modulate gene expression. It has been studied primarily in Russian academic institutions, with the evidence base consisting largely of in vitro cell culture studies and limited animal work. Pinealon is available as a supplement in some markets and is sometimes used in combination with Epitalon for purported synergistic anti-aging and neuroprotective effects.

Selank is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is a structural analogue of the immunomodulatory peptide tuftsin (Thr-Lys-Pro-Arg), extended with a C-terminal Pro-Gly-Pro sequence that confers resistance to enzymatic degradation. Selank was approved in Russia in 2009 as an anxiolytic and nootropic medication, marketed as a 0.15% nasal drop solution. The peptide is notable for its dual anxiolytic-nootropic profile — it reduces anxiety without the sedation, cognitive impairment, or dependence potential associated with benzodiazepines. Its mechanism involves modulation of GABAergic neurotransmission and immune-related gene expression rather than direct GABA receptor binding, which accounts for its distinct side effect profile. Selank is structurally and pharmacologically related to Semax, another Russian-developed neuropeptide, though the two target different receptor systems and are sometimes used in combination.

Semax is a synthetic heptapeptide derived from the N-terminal fragment of adrenocorticotropic hormone (ACTH), specifically the 4-7 sequence with a C-terminal Pro-Gly-Pro tripeptide extension that confers enzymatic stability. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and has been approved in Russia since 1996 for the treatment of stroke, cognitive disorders, and peptic ulcers. Unlike full-length ACTH, Semax lacks steroidogenic activity and exerts its effects primarily through neurotrophic and neuroprotective mechanisms. The peptide has gained attention in the nootropic community for its cognitive-enhancing properties, though the majority of clinical evidence originates from Russian-language literature. Its favorable safety profile at approved doses and non-hormonal mechanism of action distinguish it from other ACTH-derived peptides.