Nootropic

Adamax is a synthetic nootropic peptide engineered by combining two existing research compounds: the Semax heptapeptide backbone (Met-Glu-His-Phe-Pro-Gly-Pro, derived from ACTH(4-10)) and the adamantane modification strategy first demonstrated in P-21 (a CNTF-derived nootropic peptide). It carries N-terminal acetylation and a C-terminal adamantane-glycine-amide extension, distinguishing it from both standard Semax and N-Acetyl Semax Amidate. Adamax has existed as a research compound for only a few years and has no independent published research. All mechanistic claims are extrapolated from its parent compounds. It is sold exclusively through research peptide vendors and carries no regulatory approval in any jurisdiction.

Cerebrolysin is a standardized heterogeneous peptide mixture produced by controlled enzymatic hydrolysis of porcine brain cortex. It contains approximately 85% free amino acids and 15% low-molecular-weight peptide fragments (1–10 kDa) with neurotrophic properties. It is an approved pharmaceutical product in over 50 countries — including Germany (where it was developed, brand name Cerebrolysin by EVER Neuro Pharma), Austria, Russia, China, and across Eastern Europe and Asia — for the treatment of acute ischemic stroke, Alzheimer's disease, traumatic brain injury, and vascular dementia. Cerebrolysin is **not** a simple blend of known peptides and should not be categorized with vendor-formulated peptide blends. It is a complex pharmaceutical-grade biological product sold as liquid ampoules for intravenous infusion. Research peptide vendors listing it as a "lyophilized" product should be verified carefully, as this differs from the standard pharmaceutical form. Cerebrolysin is **not FDA-approved** in the United States. Clinical trial results have been mixed, with the CASTA (Cerebrolysin Acute Stroke Treatment in Asia) trial showing neurological scale improvements but also an increased early mortality signal in one analysis — a finding that has driven ongoing regulatory review and scientific debate.

Cortagen (Ala-Glu-Asp-Pro, also designated AEDP) is a synthetic tetrapeptide bioregulator identified as the primary active fraction of Cortexin, a polypeptide complex derived from bovine cerebral cortex tissue. The compound is associated with the Russian bioregulator peptide research program developed by Professor Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology. Note on nomenclature: "PDA" as a peptide designation is ambiguous. In the context of this entry, PDA is interpreted as referring to Cortagen (Ala-Glu-Asp-Pro), since this sequence matches the Ala-Glu-Asp-Pro tetrapeptide derived from Cortexin. Cortagen should not be confused with polydopamine (also abbreviated PDA in materials science contexts). Cortagen is available as a research compound primarily in Russia and Eastern Europe. It is not approved by the FDA or EMA. Its research base is primarily composed of Russian-language preclinical studies.

Dihexa (developmental code PNB-0408) is a synthetic oligopeptide derived from angiotensin IV (Ang IV), a component of the brain renin-angiotensin system. It was developed at Washington State University as an orally bioavailable, blood-brain barrier-permeable cognitive enhancer. Dihexa is a modified hexapeptide designed to bind hepatocyte growth factor (HGF) and potentiate its signaling through the c-Met receptor, a mechanism initially proposed as a potent promoter of hippocampal synaptogenesis and cognitive enhancement. **Critical research integrity concern:** The principal mechanistic paper underpinning Dihexa's mechanism of action (Benoist et al., 2014) was formally retracted in April 2025 following a Washington State University investigation finding that co-author Leen Kawas falsified western blot data. Kawas later founded Athira Pharma, which developed a Dihexa prodrug (fosgonimeton/ATH-1017) for Alzheimer's disease; the company settled False Claims Act allegations for $4 million in 2025 related to NIH grants referencing the compromised research. Despite this, some independent animal research (Sun et al., 2021) not implicated in the retraction demonstrates cognitive benefits via PI3K/AKT signaling in Alzheimer's mouse models. No human clinical trials of Dihexa have been published. Fosgonimeton (the prodrug) entered Phase 2 trials under Athira Pharma before the company's restructuring.

N-Acetyl Selank is a chemically modified variant of Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) incorporating N-terminal acetylation. Selank itself is a Russian-developed, approved synthetic heptapeptide derived from the immunomodulatory peptide tuftsin. The acetyl group is added to the N-terminus to reduce degradation by aminopeptidases, theoretically extending the active plasma half-life compared to the parent compound. N-Acetyl Selank has no independent published research — all mechanistic assumptions are extrapolated directly from the well-characterized Selank literature. It is available through research peptide vendors and is not approved for clinical use in any jurisdiction. It should be distinguished from N-Acetyl Selank Amidate (Adalank), which incorporates both N-terminal acetylation and C-terminal amidation.

N-Acetyl Selank Amidate, also marketed under the name Adalank, is a doubly modified variant of Selank incorporating both N-terminal acetylation and C-terminal amidation. These are the two standard chemical modifications applied to extend peptide half-life: N-acetylation blocks aminopeptidase degradation from the N-terminus, while C-terminal amidation mimics the natural amide bond found in many endogenous neuropeptides (including oxytocin and vasopressin) and blocks carboxypeptidase activity. Adalank is distinguished from N-Acetyl Selank (which carries only the N-terminal modification) by the additional C-terminal amide. It represents the most chemically stabilized version of the Selank peptide backbone commercially available. No independent published research exists for Adalank specifically. The compound is sold as a research peptide only and has no regulatory approval in any jurisdiction.

N-Acetyl Semax Amidate is the most chemically modified form of the Semax peptide backbone (Met-Glu-His-Phe-Pro-Gly-Pro), incorporating N-terminal acetylation and C-terminal amidation. Semax itself is a Russian-approved neuropeptide derived from ACTH(4-10) with an established clinical record for stroke and cognitive disorders. The acetyl and amidate modifications represent rational medicinal chemistry optimizations that are widely applied to improve peptide pharmacokinetics. N-Acetyl Semax Amidate has no independent published clinical research. Its evidence base is entirely derived from Semax studies. In the nootropic research community it is colloquially considered the "strongest" Semax variant due to the combined stability enhancements, though this assumption is not validated by direct comparative studies. It is sold exclusively as a research peptide with no regulatory approval.

Oxytocin is a cyclic nonapeptide neuropeptide hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus and released from the posterior pituitary. The peptide features a disulfide bond between cysteine residues at positions 1 and 6, creating a six-residue ring with a three-amino acid C-terminal tail. This structure is highly conserved across mammals and is shared with vasopressin (differing at only two positions), explaining significant cross-reactivity between the two hormone systems. Oxytocin is FDA-approved as an intravenous agent for obstetric indications. The intranasal form (Syntocinon in some countries) is approved in Europe for labor induction but is under active investigation in the United States for psychiatric applications. A substantial body of research has positioned oxytocin at the intersection of social bonding, stress regulation, neuropsychiatry, and metabolic function.

P-21 (also designated P021 or Peptide 6) is a synthetic tetrapeptide mimetic of ciliary neurotrophic factor (CNTF), a neuroprotective cytokine that promotes neuronal survival, differentiation, and plasticity. CNTF itself cannot be used therapeutically due to poor pharmacokinetics, inability to cross the blood-brain barrier, and severe systemic side effects including cachexia. P-21 was developed by identifying the minimal pharmacophore of CNTF — a DGGL tetrapeptide corresponding to residues 147-150 — and enhancing it with an adamantane modification that confers lipophilicity, metabolic stability, and blood-brain barrier permeability. P-21 is a purely preclinical compound with an entirely animal-based evidence base. No Phase 1 or Phase 2 human trials have been published. It is sold by research peptide vendors and is not approved for any clinical use. Safety in humans has not been assessed.

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.