Cerebrolysin

Cerebrolysin is a parenterally administered, peptide-based nootropic derived from purified porcine brain proteins. It is a complex mixture of low-molecular-weight peptides and amino acids designed to provide neuroprotective and neurotrophic effects.

Composition

Low-molecular-weight fraction (<10 kDa) of purified porcine brain proteins.
Contains biologically active peptides, neuropeptides, and amino acids.
Not a single, defined peptide sequence; a mixture mimicking endogenous neurotrophic factors.

Mechanism of Action

• Neurotrophic Activity: Promotes neuronal growth, sprouting, and survival, similar to naturally occurring neurotrophic factors (e.g., NGF, BDNF).
• Neuroprotection: Reduces apoptosis by modulating anti- and pro-apoptotic proteins, stabilizes calcium homeostasis, and protects neurons from ischemic and excitotoxic damage.
• Synaptic Plasticity: Enhances synaptic formation and transmission, supporting learning and memory.
• Metabolic Enhancement: Improves cerebral glucose utilization and protein synthesis.

Indications
(in use in multiple countries; not in Canada or the U.S. ):

Ischemic Stroke (acute and recovery phases)
Vascular Dementia
Alzheimer’s Disease
Traumatic Brain Injury (TBI)

DSIP

DSIP (Delta Sleep–Inducing Peptide) is an endogenous neuropeptide originally isolated from cerebral venous blood during sleep. It is a short peptide investigated for its role in sleep regulation, stress modulation, and neuroendocrine balance. DSIP is not classified as a classical hypnotic and does not act via GABAergic sedation.

 
Composition
Endogenous neuropeptide composed of 9 amino acids
Sequence: Trp–Ala–Gly–Gly–Asp–Ala–Ser–Gly–Glu
Naturally present in the central nervous system and peripheral tissues
Not a hormone; functions as a neuromodulatory peptide
 
Mechanism of Action
Sleep Architecture Modulation: Enhances slow-wave (delta) sleep without suppressing REM sleep
Neuroendocrine Regulation: Modulates pituitary hormone release, including ACTH, cortisol, and growth hormone
Stress Axis Attenuation: Reduces hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis
Neuroprotective Effects: Exhibits antioxidant properties and may reduce neuronal stress under adverse conditions
Autonomic Stabilization: Supports balance between sympathetic and parasympathetic activity
 
Indications
(Investigational / clinical use varies by country; not approved in Canada or the U.S.)

Insomnia and sleep–wake rhythm disturbances
Stress-related fatigue and burnout states
Adaptation disorders (e.g., jet lag, shift work)
Adjunctive support in neurodegenerative and stress-mediated conditions
Chronic pain and withdrawal-related sleep disruption

PE-22-28

PE-22-28 is a synthetic 7–amino acid fragment derived from the C-terminus of pituitary adenylate cyclase-activating polypeptide (PACAP), designed to retain neuroprotective effects while reducing activation of the primary PACAP receptor.

Structure

7–amino acid sequence: Leu-Ser-Ala-Leu-Leu-Ser-Leu
Derived from the C-terminal region of PACAP, engineered to selectively modulate receptor activity and minimize side effects.

Mechanism of Action

• Receptor Modulation: Acts as a partial agonist at the PAC1 receptor, triggering neuroprotective signaling pathways (e.g., MAPK/ERK) without producing the full cAMP response of full-length PACAP.
• Neuroprotection: Promotes neuronal survival, reduces brain inflammation, and protects against oxidative stress and excitotoxicity.
• Reduced Side Effects: By avoiding strong G-protein (cAMP) activation, it may limit hypotension, tachycardia, and other PACAP-related side effects.

Indications
(Preclinical and investigational uses):

Neurodegenerative Diseases (e.g., Alzheimer’s, Parkinson’s)
Ischemic Stroke
Traumatic Brain and Spinal Cord Injury

Selank

Selank is a synthetic heptapeptide analog of the endogenous immunomodulatory peptide tuftsin, known for its anxiolytic and nootropic effects without the sedative or muscle-relaxant properties of traditional benzodiazepines.

Structure

7–amino acid sequence: Thr-Lys-Pro-Arg-Pro-Gly-Pro
Synthetic analog of tuftsin, designed to retain immunomodulatory and neuromodulatory activity.

Mechanism of Action

• GABA System Modulation: Modulates GABA expression and degradation, producing a calming, anxiolytic effect.
• Serotonin and Dopamine Regulation: Adjusts monoamine neurotransmitter levels, contributing to mood stabilization and anti-anxiety effects.
• Enkephalinase Inhibition: Protects endogenous enkephalins from degradation, prolonging their positive neuromodulatory effects.
• Immune Modulation: Influences immune system activity, linking immunomodulation to effects on anxiety and stress-related behaviors.

Research Indications:

Anxiety Disorders and Generalized Anxiety
Depression (adjunct therapy)
Neurotic and Stress-Related Conditions
Cognitive Enhancement under Stress

 

Semax

Semax is a synthetic heptapeptide analog of the ACTH(4-10) fragment, designed as a potent nootropic and neuroprotective agent without corticotropic (hormone-releasing) activity.

Structure

7–amino acid sequence: Met-Glu-His-Phe-Pro-Gly-Pro
Features a C-terminal Pro-Gly-Pro tripeptide extension to enhance stability and potency.
Synthetic analog of ACTH(4-10), retaining neuroprotective and cognitive-enhancing properties.

Mechanism of Action

• BDNF Upregulation: Increases expression of Brain-Derived Neurotrophic Factor (BDNF), supporting neuronal survival, plasticity, and cognitive function.
• Neurotrophic Effects: Enhances neurotrophin activity (e.g., NGF, BDNF) and receptor functionality.
• Neurotransmitter Modulation: Influences dopaminergic, serotonergic, and GABAergic pathways, improving attention, learning, and memory.
• Cerebrovascular Improvement: Increases cerebral blood flow and provides antioxidant protection against ischemia and oxidative stress.

Research Indications:

Ischemic Stroke and Transient Ischemic Attack (TIA)
Cognitive and Memory Disorders
Optic Nerve Atrophy and Glaucoma
Off-label: Cognitive enhancement and focus