Microglia: nootropics and compounds | sci-wiki

Cordycepin

Cordycepin, also known as 3'-deoxyadenosine, is a nucleoside analog of adenosine in which the hydroxyl group at the 3' position of the sugar is replaced by hydrogen. It was first isolated in 1950 from the entomopathogenic fungus Cordyceps militaris, and it also occurs in related fungi and can now be produced synthetically. Because it closely resembles adenosine, cordycepin can slip into biochemical pathways in place of the natural nucleoside, an ability that underlies its studied antitumor, anti-inflammatory, and antiviral properties.

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Nootropic

Emapunil

Emapunil (developmental codes XBD-173 and AC-5216) is an investigational anxiolytic that acts as a selective, high-affinity agonist of the 18-kDa translocator protein (TSPO), a mitochondrial cholesterol-transport protein once known as the peripheral or mitochondrial benzodiazepine receptor. Rather than binding the central benzodiazepine site itself, emapunil stimulates the brain's own synthesis of neurosteroids, most notably allopregnanolone, which then potentiate GABA-A receptors (the brain's main inhibitory chloride channels) to produce anxiolysis. In a landmark 2009 human panic-provocation study it reduced induced anxiety without the sedation, tolerance, or withdrawal that characterise benzodiazepines. It reached Phase 2 clinical evaluation before development was discontinued, and it remains a widely cited proof of concept for neurosteroid-based anxiolysis.

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Cannabinoid

HU-308

HU-308 is a synthetic cannabinoid that acts as a highly selective agonist of the type-2 cannabinoid receptor (CB2), the peripheral and immune-cell arm of the endocannabinoid system. First reported in 1999 by Raphael Mechoulam's group at the Hebrew University of Jerusalem, it was designed as a nonpsychotropic probe: it binds CB2 with nanomolar affinity (Ki ~22.7 nM) while showing essentially no affinity for the centrally expressed CB1 receptor (Ki > 10 microM), so it produces none of the tetrahydrocannabinol-type behavioral effects mediated by CB1. Through CB2 activation it lowers blood pressure, blocks defecation, and exerts anti-inflammatory and peripheral analgesic activity, effects reversed by the CB2 antagonist SR-144528 but not by the CB1 antagonist rimonabant. Across preclinical models it dampens pro-inflammatory cytokine release from macrophages and microglia, and it has been studied in acute lung injury, collagen-induced arthritis, endothelial activation, Parkinsonian neuroinflammation, and proliferative vitreoretinopathy. HU-308 remains an investigational research compound and is not an approved drug.

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Neuroprotection

Ibudilast

Ibudilast (MN-166, Ketas) is a brain-penetrant, multi-target neuroimmune modulator that stands apart from the pure PDE4 crowd. It inhibits several phosphodiesterases (PDE3/4/10/11) while also blocking macrophage migration inhibitory factor (MIF) and toll-like receptor 4 (TLR4), quieting overactive glia and shifting cytokines toward repair. Marketed for decades in Japan for asthma and post-stroke dizziness, it has advanced internationally as MN-166 through progressive MS, ALS and addiction trials.

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Nootropic

Fingolimod

Fingolimod is a sphingosine-1-phosphate receptor modulator used to treat relapsing forms of multiple sclerosis. Approved in 2010 and sold as Gilenya, it was the first oral disease-modifying therapy for the condition, offering an alternative to injections for many patients. It works by trapping immune cells in the lymph nodes so that fewer of them can reach and attack the brain and spinal cord.

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