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Every compound in the sci-wiki that affects hippocampus; 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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MAP4343 (3β-methoxypregnenolone) is a synthetic derivative of the endogenous neurosteroid pregnenolone in which the 3β-hydroxyl group is replaced by a methyl ether, developed by the French steroid pharmacologist Étienne-Émile Baulieu and the biotechnology company Mapreg. Unlike classical neurosteroids that modulate ligand-gated ion channels, MAP4343 acts on microtubule-associated protein 2 (MAP2; a structural protein that governs the assembly and stability of neuronal microtubules), where it promotes tubulin polymerization and restores microtubule dynamics. It has been investigated as a novel, mechanistically distinct antidepressant and anti-addiction candidate, showing rapid and durable antidepressant-like effects in rodent and tree shrew stress models and having advanced into early clinical development. As of the mid-2020s it remains an investigational agent without regulatory approval.
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.