Cognitive & Nootropic

FGL (Fibroblast Growth Loop) is a synthetic 15-amino acid peptide derived from the second fibronectin type III module of Neural Cell Adhesion Molecule (NCAM) that functions as an NCAM mimetic by binding to and activating fibroblast growth factor receptor 1 (FGFR1). This peptide has demonstrated extensive neuroprotective, neurotrophic, and anti-inflammatory effects in preclinical studies, including mobilization of neural stem cells, enhancement of synaptic plasticity, and protection against ischemic and amyloid-beta-induced neuronal damage. FGL has advanced to early-stage human clinical trials for neurodegenerative diseases, showing favorable safety and tolerability profiles in Phase I studies with intranasal administration.

Delta Sleep-Inducing Peptide (DSIP) is a naturally occurring nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) with molecular weight 848.824 Da, first isolated from rabbit cerebral venous blood in 1974. It functions as a neuromodulatory peptide found in the hypothalamus, limbic system, pituitary, and peripheral organs, crossing the blood-brain barrier easily without enzymatic degradation. DSIP's primary mechanisms involve modulation of sleep architecture, neurotransmitter regulation (serotonin, dopamine, glutamate), stress response via the HPA axis, and potential interaction with NMDA receptors and adrenergic pathways. Clinical applications have focused on chronic insomnia, stress-related disorders, pain management, and substance withdrawal symptoms, though exact mechanisms remain incompletely characterized. Despite 50 years of research, DSIP is not FDA-approved or regulated by major health authorities worldwide, remaining available only as a research compound. It exists in an unregulated gray market, with most commercially available forms being research-grade material not intended for human use, and the FDA has flagged it for potential immunogenicity risks.

Selank is a synthetic heptapeptide anxiolytic and nootropic drug developed by the Institute of Molecular Genetics of the Russian Academy of Sciences. It is a synthetic analog of the immunomodulatory peptide tuftsin, consisting of the tuftsin sequence (Thr-Lys-Pro-Arg) elongated at the C-terminus with Pro-Gly-Pro for enhanced metabolic stability. Selank exhibits pronounced anxiolytic, nootropic, neuroprotective, and immunomodulatory activities through modulation of GABAergic, serotonergic, and dopaminergic neurotransmitter systems, along with regulation of brain-derived neurotrophic factor (BDNF) expression.

Semax is a synthetic heptapeptide analog of adrenocorticotropic hormone (ACTH), specifically derived from the ACTH(4-10) fragment, with the amino acid sequence Met-Glu-His-Phe-Pro-Gly-Pro. Developed in Russia, it exhibits pronounced nootropic, neuroprotective, and neurotrophic properties without hormonal activity. The peptide works through multiple mechanisms including modulation of brain-derived neurotrophic factor (BDNF) expression, enhancement of dopamine and serotonin levels, melanocortin receptor interaction, and anti-inflammatory effects. Research demonstrates efficacy in treating acute ischemic stroke, cognitive impairment, optic nerve diseases, and peptic ulcers. Clinical trials in Russia have shown improvements in neurological recovery, memory, attention, and neuroprotection. Semax is approved and marketed as a prescription medication in Russia and Eastern Europe, where it has been in clinical use since the 1990s. However, it has not been evaluated or approved by regulatory agencies in the United States, European Union, United Kingdom, or most other countries, where it is sold only as a research chemical.

Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Pro) derived from brain cortex polypeptide extract Cortexin, developed by Vladimir Khavinson as part of the peptide bioregulator family. It demonstrates neuroprotective properties through epigenetic gene regulation, promotes nerve regeneration, and crosses the blood-brain barrier to exert direct CNS effects. Research shows it increases nerve fiber growth rate by 27% and conduction velocity by 40%, while modulating gene expression across 110+ genes involved in neural repair, cardiovascular function, and cellular differentiation.

Pinealon (EDR) is a synthetic tripeptide bioregulator composed of glutamic acid, aspartic acid, and arginine (Glu-Asp-Arg) developed by Russian scientist Vladimir Khavinson. Originally isolated from the polypeptide neuroprotective drug Cortexin, it demonstrates potent neuroprotective properties through multiple mechanisms including ROS suppression, gene expression regulation, and epigenetic modulation. Pinealon has been extensively studied in Russian scientific literature for its effects on cognitive function, neuroplasticity, and cellular aging processes.

Cerebrolysin is a parenterally administered neuropeptide preparation derived from purified porcine brain proteins through controlled enzymatic digestion. Composed of low molecular weight peptides (25%) and free amino acids (75%), it contains over 14,000 identified peptides corresponding to more than 1,600 porcine neuronal proteins. Cerebrolysin exhibits pharmacodynamic properties similar to endogenous neurotrophic factors, demonstrating neuroprotective and neurorestorative effects across multiple neurological conditions. The preparation has been extensively studied in clinical trials for acute ischemic stroke, traumatic brain injury, Alzheimer's disease, vascular dementia, and amyotrophic lateral sclerosis. While approved in over 50 countries including Austria, China, Germany, Russia, and South Korea, it remains unapproved by the FDA in the United States. Clinical evidence suggests potential benefits for cognitive function, neurological recovery, and functional outcomes, though results vary across different meta-analyses and patient populations.

Dihexa (PNB-0408) is a small-molecule, orally active angiotensin IV analog developed at Washington State University that functions as a potent hepatocyte growth factor (HGF) mimetic. It binds with high affinity to HGF (Kd=65 pM) and potentiates its activity at the c-Met receptor, stimulating synaptogenesis and neurogenesis at picomolar concentrations. Preclinical research demonstrates that Dihexa is seven orders of magnitude more potent than brain-derived neurotrophic factor (BDNF) at promoting synaptic connectivity. The compound crosses the blood-brain barrier, making it highly bioavailable compared to native HGF. In animal models, Dihexa has shown remarkable efficacy in reversing cognitive deficits, restoring motor function in Parkinson's disease models, and protecting against neurodegeneration through activation of the PI3K/AKT signaling pathway. The prodrug fosgonimeton (ATH-1017) entered clinical trials for Alzheimer's and Parkinson's disease but failed Phase 2/3 trials in 2024. Despite promising preclinical data, no human studies of Dihexa itself have been published, and significant safety concerns exist regarding potential cancer risk from c-Met activation. Dihexa remains an experimental research compound without regulatory approval in any country.

P21 (also known as P021) is a synthetic tetrapeptide (Ac-DGGLAG-NH2) derived from the biologically active region of human ciliary neurotrophic factor (CNTF; amino acid residues 148-151). An adamantylated glycine is added to its C-terminal to enhance blood-brain barrier permeability and reduce degradation by exopeptidases. P21 promotes neurogenesis in the hippocampal dentate gyrus by competitively inhibiting the leukemia inhibitory factor (LIF) signaling pathway and increasing brain-derived neurotrophic factor (BDNF) expression. Preclinical studies demonstrate P21's ability to enhance learning, memory, and synaptic plasticity while reducing tau hyperphosphorylation and amyloid-beta pathology in Alzheimer's disease models. The compound exhibits favorable pharmacokinetics for oral administration with minimal adverse effects compared to full-length CNTF.

N-Acetyl Selank is an enhanced synthetic heptapeptide derived from the endogenous immune peptide tuftsin, featuring acetylation for improved stability and bioavailability. It functions as a potent anxiolytic and nootropic compound with demonstrated effects on GABAergic, dopaminergic, and serotonergic neurotransmission. Originally developed by the Institute of Molecular Genetics of the Russian Academy of Sciences and approved for anxiety disorder treatment in Russia, it exhibits neuroprotective, immunomodulatory, and cognitive-enhancing properties without the side effects typical of benzodiazepines.

N-Acetyl Semax Amidate is a modified and enhanced version of the Russian nootropic peptide Semax, incorporating both N-terminal acetylation and C-terminal amidation modifications. This dual modification dramatically improves pharmacokinetic properties compared to standard Semax, including enhanced metabolic stability, extended half-life (6-12 hours vs 2-4 hours), superior bioavailability, and increased resistance to enzymatic degradation. The peptide is based on Semax, a synthetic heptapeptide analog of ACTH(4-10) with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. N-Acetyl Semax Amidate exhibits pronounced nootropic, neuroprotective, and neurotrophic properties through multiple mechanisms including upregulation of brain-derived neurotrophic factor (BDNF) expression, enhancement of dopamine and serotonin neurotransmission, melanocortin receptor modulation, and anti-inflammatory effects. While the parent compound Semax has extensive clinical research demonstrating efficacy in stroke recovery, cognitive enhancement, and neuroprotection, specific clinical trials on N-Acetyl Semax Amidate remain limited. The compound is primarily used as a research chemical and has not been evaluated or approved by regulatory agencies including the FDA, making it available only for research purposes in most countries outside Russia.