Neuroactive steroids

• DOI: 10.1096/fasebj.6.6.1347506
• Publication Date: 2018-01-25T10:17:07Z
• Authors: Steven M. Paul; Robert H. Purdy
• Keywords: Allopregnanolone; Pregnanolone; Picrotoxin; Pregnenolone sulfate; Pregnane; Convulsants

Neuroactive steroids are natural or synthetic that rapidly alter the excitability of neurons by binding to membrane-bound receptors such as those for inhibitory and (or) excitatory neurotransmitters. The best-studied neuroactive a series sedative-hypnotic 3α-hydroxy ring A-reduced pregnane include major metabolites progesterone deoxycorticosterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), respectively. These 3α-hydroxysteroids do not interact with classical intracellular steroid but bind stereoselectively high affinity neurotransmitter in brain, γ-aminobutyric acid (GABA). Biochemical electrophysiological studies have shown these markedly augment GABA-activated chloride ion currents manner similar (but identical) anesthetic barbiturates. Several also been observed convulsant proconvulsant properties, including amidine 3α-hydroxy-16-imino-5β-17-azaandrostan-11-one (RU5135) sulfate esters pregnenolone dehydroepiandrosterone. be bicuculline picrotoxin-like GABAA receptor antagonists. Examples neuronal augmenting inhibiting amino receptor-mediated responses reported. Recently, allopregnanolone allotetrahydroDOC measured brain plasma where their levels fluctuate response stress during estrous menstrual cycles rats humans, Although fraction tissue, is adrenal and/or ovarian origin, appreciable can still brains adrenalectomized oophorectomized animals. Receptor-active neurosteroids may represent an important class neuromodulators central nervous system via novel nongenomic mechanisms.—Paul, S. M.; Purdy, R. H. steroids. FASEB J. 6: 2311-2322; 1992.