long-term potentiation

Every compound in the sci-wiki that affects long-term potentiation; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

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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.

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Nootropic

Pregnenolone Sulfate

Pregnenolone sulfate (PregS) is an endogenous excitatory neurosteroid (a steroid synthesized in and acting upon the nervous system) formed by sulfation of pregnenolone at its 3beta-hydroxyl group. It is among the most intensively studied neurosteroids in ion-channel pharmacology, acting simultaneously as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors that contain GluN2A or GluN2B subunits (the principal glutamate-gated channels underlying synaptic plasticity), a negative allosteric modulator of GABA-A receptors (the brain's main inhibitory chloride channels), a low-affinity agonist of the sigma-1 receptor (an intracellular chaperone protein) and the prototypical agonist of the TRPM3 cation channel. Through these convergent actions it enhances glutamatergic transmission, hippocampal acetylcholine release, long-term potentiation and memory consolidation in animal models, which underlies its reputation as a pro-cognitive neurosteroid. Its physiological concentrations, and even its unambiguous presence in mammalian brain, remain debated, so much of the evidence base derives from experimental administration rather than demonstrated endogenous signaling.

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