Cognition .

Semax is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is structurally derived from the ACTH(4-7) sequence (Met-Glu-His-Phe) with an additional Pro-Gly-Pro sequence that increases enzymatic stability. In preclinical studies, interactions with the melanocortin system (MC4R), BDNF expression and the dopaminergic system have been described. Administered intranasally, Semax crosses the blood-brain barrier in animal models. Postulated effects include modulation of learning and memory processes and neuroprotective properties.

CognitionImmunomodulation

Other

Selank

TP-7

Selank is a synthetic heptapeptide, likewise developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is based on the sequence of the endogenous immunomodulator tuftsin (Thr-Lys-Pro-Arg) with a C-terminal Pro-Gly-Pro extension for enzymatic stabilisation. In preclinical studies, anxiolytic effects without sedative properties have been described — compared with benzodiazepines, no GABA-A modulatory mechanism was demonstrated. Possible mechanisms discussed include modulation of the serotonergic system, inhibition of enkephalin degradation, and immunomodulatory effects via tuftsin receptors.

DSIP

Delta Sleep-Inducing Peptide

preclinicalDE: unclassified

DSIP is a nonapeptide (sequence: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) isolated in 1977 from the thalamic venous blood of rabbits. Its molecular mechanisms of action remain incompletely understood. Interactions with GABA receptors, a modulating effect on the hypothalamic-pituitary axis and neuroprotective properties via antioxidant pathways have been discussed. In animal experiments, changes in the sleep EEG were observed after intracerebroventricular administration; whether this translates to systemic administration in humans is unclear.

ImmunomodulationCognition

VIP

Vasoaktives Intestinales Peptid

VIP is a 28-amino-acid neuropeptide of the secretin/glucagon superfamily, produced throughout the nervous system as well as in intestinal, respiratory and immunological tissues. VIP binds the G-protein-coupled receptors VPAC1 and VPAC2, which via cAMP signalling pathways leads to vasodilation, bronchodilation and pronounced immunomodulation. Immunologically, VIP inhibits the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-12) and promotes regulatory T cells (Tregs) as well as anti-inflammatory mediators (IL-10). In the lung and gut, VIP also acts as a neuroprotective and epithelium-protecting mediator.

Oxytocin

early clinical studiesDE: prescription-only

Oxytocin is a cyclic nonapeptide produced in the hypothalamus and released via the neurohypophysis. Peripherally it acts at oxytocin receptors of the uterus (labour) and the mammary gland (milk ejection). In the central nervous system it is investigated in the context of social behaviour, bonding, trust and stress regulation. Its short half-life and limited passage of the blood–brain barrier are methodologically relevant.

Cerebrolysin

CognitionRecovery

Cerebrolysin is not a single peptide but a standardised mixture of low-molecular-weight peptides and free amino acids derived from porcine brain tissue. It is credited with neurotrophic and neuroprotective properties said to resemble those of the body's own neurotrophic factors. Discussed effects include neuronal survival, synaptic plasticity and modulation of inflammatory and apoptotic processes. Its exact composition and mechanism of action are not fully characterised.

Anti-agingCognitionMetabolism

Mitochondrial peptide

Humanin

Humanin is a short, mitochondrially encoded peptide (mitochondrial-derived peptide, MDP) originating from a reading-frame region of the mitochondrial 16S rRNA. It is credited with cytoprotective and anti-apoptotic properties, partly via interactions with receptor complexes and Bcl-2-associated signalling. In preclinical models humanin has been investigated in the context of neuronal protection, insulin sensitivity and aging processes. The synthetic analog HNG shows enhanced activity.

Dihexa

Dihexa is a small angiotensin IV-derived peptide analog modified for improved stability and membrane permeability. In preclinical work it is linked to hepatocyte growth factor (HGF) and its receptor c-Met and is said to promote synapse formation (synaptogenesis). It has been investigated in the context of learning and memory performance in animal models. The precise molecular mechanism is the subject of research.

Other

Adalank

Adalank is a chemically modified variant of the heptapeptide Selank, with an acetylated N-terminus and an amidated C-terminus. These modifications are intended to improve stability against enzymatic degradation and the pharmacokinetics relative to the parent peptide. Its assumed mechanism corresponds to that of Selank (tuftsin-derived, discussed as anxiolytic without a classic GABA-A mechanism). However, there is no independent evidence of efficacy for the modified form itself.

P021

P021 is a small, peptidomimetic molecule derived from an active region of ciliary neurotrophic factor (CNTF). It is designed to be metabolically stable and able to cross the blood–brain barrier. In preclinical models it is credited with promoting neurogenesis and neurotrophic signalling (including BDNF) and inhibiting pathological tau changes. It is investigated in the context of Alzheimer's models.

PE-22-28

PE-22-28 is a shortened analog of spadin, an endogenous peptide derived from the propeptide of the sortilin/neurotensin receptor 3. It inhibits the potassium channel TREK-1, which is involved in mood regulation and depression. In preclinical models a rapid antidepressant effect and promotion of neurogenesis and synaptogenesis are described. PE-22-28 was developed as a more stable, more bioavailable spadin derivative.