Description
Allopregnanolone is an endogenous inhibitory pregnane neurosteroid that is synthesized from progesterone . It acts as a positive allosteric modulator of GABA
A receptors at nM concentrations (exhibiting the greatest potentiation at isoforms containing δ subunits) and of GABA
C receptors at μM concentrations. Allopregnanolone displays effects similar to other GABA
A receptor potentiators such as benzodiazepines, including potent anticonvulsant, anxiolytic, and sedative activity.
Uses
(3α)-Allopregnanolone acts as a GABAA receptor positive allosteric modulator. (3α)-Allopregnanolone is a metabolite of Progesterone (P755900). (3α)-Allopregnanolone is a neuroactive steroid present in the blood and also the brain.
Definition
ChEBI: Brexanolone is a 3-hydroxy-5alpha-pregnan-20-one in which the hydroxy group at position 3 has alpha-configuration. It is a metabolite of the sex hormone progesterone and used for the treatment of postpartum depression in women. It has a role as a human metabolite, an antidepressant, a GABA modulator, an intravenous anaesthetic and a sedative.
Biological Activity
GABA A receptor positive allosteric modulator. Neuroactive steroid.
Synthesis
synthesis of Brexanolone
References
[1] MARIA LUISA BARBACCIA . Endogenous γ-aminobutyric acid (GABA)A receptor active neurosteroids and the sedative/hypnotic action of γ-hydroxybutyric acid (GHB): A study in GHB-S (sensitive) and GHB-R (resistant) rat lines[J]. Neuropharmacology, 2005, 49 1: Pages 48-58. DOI:
10.1016/j.neuropharm.2005.01.026[2] REDDY D S. Neurosteroids: endogenous role in the human brain and therapeutic potentials.[J]. Progress in brain research, 2010, 186: 113-137. DOI:
10.1016/b978-0-444-53630-3.00008-7[3] ARIELA FRIEDER. Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development.[J]. CNS drugs, 2019, 33 3: 265-282. DOI:
10.1007/s40263-019-00605-7[4] IRINA BALAN. Endogenous Neurosteroid (3α,5α)3-Hydroxypregnan-20-one Inhibits Toll-like-4 Receptor Activation and Pro-inflammatory Signaling in Macrophages and Brain.[J]. Scientific Reports, 2019: 1220. DOI:
10.1038/s41598-018-37409-6[5] YI CHANG. Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals.[J]. Synapse, 2019, 73 3: e22076. DOI:
10.1002/syn.22076[6] INJA CHO. Increased Superoxide Dismutase 2 by Allopregnanolone Ameliorates ROS-Mediated Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus[J]. Neurochemical Research, 2018, 43 7: 1464-1475. DOI:
10.1007/s11064-018-2561-4
