Neuroprotection: nootropics and compounds | sci-wiki

EPObis

EPObis is a synthetic dendrimeric peptide designed from the binding Site 1 sequence of human erythropoietin, guided by the crystal structure of the erythropoietin-receptor complex. It binds the erythropoietin receptor and reproduces the cytokine's tissue-protective signaling; in cultured neurons it promotes neurite outgrowth and survival in a receptor-dependent manner. Unlike erythropoietin itself, EPObis is non-erythropoietic, so it activates protective pathways without stimulating red blood cell production, and after systemic administration it crosses the blood-brain barrier into the cerebrospinal fluid. In rodent studies it reduces tumor necrosis factor release from activated macrophages and microglia, delays clinical signs in experimental autoimmune encephalomyelitis, and enhances working memory, marking it as an experimental neuroprotective and anti-inflammatory research peptide.

2 outlets

Nootropic

N-PEP-12

N-PEP-12 is an oral dietary supplement of small brain-derived peptides and free amino acids, sold as Memoprove and described by its own investigators as a lower-potency, needle-free relative of the injectable neurotrophic drug Cerebrolysin. Small, mostly manufacturer-linked studies report modest short-term gains in memory and brain EEG activity in aging adults and in stroke recovery. It is an appealing, gentle nootropic idea, but the human evidence is thin and largely industry-linked, and the core assumption that oral brain peptides survive digestion to reach the brain remains pharmacologically unproven.

1 outlet

Nootropic

Taltirelin

Taltirelin (TA-0910, brand name Ceredist) is a synthetic, metabolically stable analog of thyrotropin-releasing hormone (TRH), the three-residue hypothalamic peptide. It was developed by Tanabe Seiyaku and approved in Japan in 2000 for spinocerebellar degeneration, where it is taken orally to help with ataxia and related symptoms. The interesting thing about taltirelin is that it was engineered to keep the central nervous system effects of TRH while shedding most of the hormonal ones; it is roughly 10 to 100 times more potent than native TRH at driving CNS arousal, yet its effect on thyroid hormone release is much weaker. It also lasts far longer in the body because it resists the enzymes that chew up natural TRH within minutes. Outside its approved use it gets discussed in nootropic and biohacker circles as a wakefulness-promoting, pro-cholinergic "analeptic" and neuroprotective agent, and there is a real preclinical literature behind those claims (Parkinson's models, ischemia, pain, respiratory stimulation). Human data outside spinocerebellar degeneration is thin, so most of what you read about it as a cognitive enhancer is extrapolation from animal work.

1 outlet

Nootropic

7,8-DHF

7,8-Dihydroxyflavone (7,8-DHF), also called tropoflavin, is a naturally occurring flavone studied as a small-molecule mimic of brain-derived neurotrophic factor (BDNF). It is reported to act as an agonist of tropomyosin receptor kinase B (TrkB), the principal BDNF receptor, binding the receptor's extracellular domain to drive its dimerization and activation, and because it is orally active and crosses the blood-brain barrier it has become a widely used tool compound in neuroscience. Its direct activation of TrkB is not fully settled, however, since some quantitative assays have been unable to reproduce it, and it remains an experimental compound studied in models of depression, Alzheimer's, and other neurological conditions.

2 outlets

Nootropic

DHEA

Dehydroepiandrosterone (DHEA) is an endogenous androstane neurosteroid and the most abundant circulating steroid hormone in humans, secreted chiefly by the adrenal cortex and also synthesized de novo within the central nervous system. It functions primarily as a precursor to androgens and estrogens, yet exerts direct actions on the brain by acting as an agonist at the sigma-1 receptor (an endoplasmic reticulum chaperone protein that shapes calcium and neurotrophic signaling), as a positive modulator of NMDA receptor (the principal excitatory glutamate ion channel involved in learning) signaling, and, chiefly as its sulfate ester DHEAS, as a negative allosteric modulator of the GABA-A receptor (the brain's main inhibitory ion channel). DHEA additionally behaves as a functional anti-glucocorticoid, buffering the neurotoxic effects of cortisol, and shows neuroprotective and mood-related activity in preclinical and clinical studies. Circulating concentrations peak in early adulthood and decline markedly with age, a phenomenon termed adrenopause that has driven its widespread use as an over-the-counter supplement.

2 outlets

Mitochondrial

Indolepropionamide

Indolepropionamide (IPAM) is a naturally occurring indole compound, chemically related to melatonin, that has been studied as a mitochondrial protectant and antioxidant. In laboratory research it was reported to stabilize energy production in mitochondria, lower the output of reactive oxygen species, and extend lifespan in a simple invertebrate model. It remains an investigational substance with limited study rather than an approved medicine.

1 outlet

Supplement

Lithium Orotate

Lithium orotate is a salt of lithium and orotic acid sold as a low-dose dietary supplement. It provides much less elemental lithium per tablet than the lithium carbonate used as a prescription mood stabilizer, and it is marketed for mood and general wellbeing. It is not approved as a medicine, and rigorous human evidence for its benefits is lacking.

1 outlet

Nootropic

Rosemary Extract

Rosemary extract is a concentrated preparation of the culinary herb Rosmarinus officinalis (now often classed as Salvia rosmarinus). Its active fraction is dominated by two polyphenols; carnosic acid, a fat-soluble diterpene that activates the body's own antioxidant defenses, and rosmarinic acid, a water-soluble caffeic acid ester. The plant's volatile oil also carries 1,8-cineole, the aromatic component tied to rosemary's cognitive reputation. It's studied mostly for memory support, antioxidant activity, and mild mood effects.

1 outlet

Hormone

Progesterone

Progesterone (P4; pregn-4-ene-3,20-dione) is an endogenous pregnane steroid hormone best known for its reproductive roles and is the prototypical neuroactive precursor within the neurosteroid system. Although the parent hormone signals principally through classical nuclear progesterone receptors and through membrane-associated receptors such as PGRMC1 and the mPR/PAQR family, most of its rapid effects on neuronal excitability arise only after sequential metabolism to 5-alpha-dihydroprogesterone and then to allopregnanolone, one of the most potent endogenous positive allosteric modulators of the GABA-A receptor (the brain's principal inhibitory chloride channel). Progesterone and its metabolites are synthesized within the nervous system itself, where they regulate myelination, neuronal survival, neuroinflammation, and inhibitory tone. It has been studied extensively as a neuroprotective agent, with strong preclinical support but negative large-scale human trials in acute traumatic brain injury.

2 outlets

Nootropic

24(S)-Hydroxycholesterol

24(S)-Hydroxycholesterol (historically named cerebrosterol) is an endogenous oxysterol (an oxygenated derivative of cholesterol) generated almost exclusively in neurons by the enzyme cholesterol 24-hydroxylase (CYP46A1). It is the principal chemical route by which the brain, which cannot degrade cholesterol, exports its surplus; because the added hydroxyl group at carbon 24 allows the molecule to cross the blood-brain barrier (the selective interface between blood and brain tissue), plasma levels of 24(S)-hydroxycholesterol serve as an accessible marker of brain cholesterol turnover and neuronal mass. Beyond its housekeeping role, it is a bona fide neurosteroid; at physiological concentrations it acts as a potent positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors (a class of glutamate-gated ion channels central to learning and memory) and as an agonist of liver X receptors (LXR, nuclear receptors that govern lipid handling). Its pharmacology inspired the synthetic analog dalzanemdor (SAGE-718), an NMDA receptor positive allosteric modulator developed for cognitive impairment.

Neuroprotection

EPObis

N-PEP-12

Taltirelin

7,8-DHF

DHEA

Indolepropionamide

Lithium Orotate

Rosemary Extract

Progesterone

24(S)-Hydroxycholesterol

Androstenediol

Colivelin

Davunetide

DHEA Sulfate

Etazolate

Ethomersol

HNG (S14G-Humanin)

Homotaurine

LM22A-4

MIF-1 (Melanostatin)

PRE-084

Rapastinel

Tetrahydrocannabinolic acid

VD11

Fingolimod

Neotrofin

DHED

Neuroprotection

EPObis

N-PEP-12

Taltirelin

7,8-DHF

DHEA

Indolepropionamide

Lithium Orotate

Rosemary Extract

Progesterone

24(S)-Hydroxycholesterol

Androstenediol

Colivelin

Davunetide

DHEA Sulfate

Etazolate

Ethomersol

HNG (S14G-Humanin)

Homotaurine

LM22A-4

MIF-1 (Melanostatin)

PRE-084

Rapastinel

Tetrahydrocannabinolic acid

VD11

Fingolimod

Neotrofin

DHED