Neurosteroids

Introduction & definition

• Neurosteroids (neuroactive steroids) are steroid molecules that rapidly alter neuronal excitability by non-genomic membrane actions — chiefly allosteric modulation of ligand-gated ion channels — rather than the slow genomic action of classical steroid hormones.
• Terminology — neurosteroid (Baulieu) = steroid synthesised de novo within the nervous system; neuroactive steroid = any steroid (CNS-, peripherally-derived or synthetic) that is pharmacologically active on neuronal targets — used interchangeably in regulatory labelling.
• Core action — the therapeutically exploited effect is positive allosteric modulation (PAM) of the GABA_A receptor, the principal inhibitory ionotropic receptor of the CNS — the same complex on which benzodiazepines and barbiturates act, but at a pharmacologically distinct steroid-recognition site.
• Clinical relevance — the first mechanistically novel GABAergic drug class in decades — validated by three FDA approvals (2019–2023) across mood disorders (brexanolone, zuranolone) and epilepsy (ganaxolone).