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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H34O2
Molecular Weight 318.4935
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BREXANOLONE

SMILES

CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C

InChI

InChIKey=AURFZBICLPNKBZ-SYBPFIFISA-N
InChI=1S/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14-,15+,16-,17+,18-,19-,20-,21+/m0/s1

HIDE SMILES / InChI

Description

Allopregnanolone is a neurosteroid metabolite of progesterone. It is an allosteric modulator of inhibitory γ-aminobutyric acid (GABA-A) receptors on neural stem cells and other cell types in the brain. Allopregnanolone has effects similar to those of other positive allosteric modulators of the GABA action at GABAA receptor such as the benzodiazepines, including anxiolytic, sedative, and anticonvulsant activity. A solution of allopregnanolone, SAGE-547 is an intravenous allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid type A (GABAA)receptors. It's believed that allopregnanolone is effective as an anticonvulsant when prolonged seizure activity has become resistant to benzodiazepine treatment. Under the names brexanolone and SAGE-547, allopregnanolone is under development by SAGE Therapeutics as an intravenously administered drug for the treatment of super-refractory status epilepticus, postpartum depression, and essential tremor. Allopregnanolone is in phase III trials for the treatment of super-refractory status epilepticus (SRSE) and postpartum depression.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine.
1998 Mar 17
Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.
1998 Oct 13
Profiling neurosteroids in cerebrospinal fluids and plasma by gas chromatography/electron capture negative chemical ionization mass spectrometry.
2000 Jan 15
Neuroactive ring A-reduced metabolites of progesterone in human plasma during pregnancy: elevated levels of 5 alpha-dihydroprogesterone in depressed patients during the latter half of pregnancy.
2001 Dec
Progesterone withdrawal increases the alpha4 subunit of the GABA(A) receptor in male rats in association with anxiety and altered pharmacology - a comparison with female rats.
2002 Sep
The influence of subunit composition on the interaction of neurosteroids with GABA(A) receptors.
2002 Sep
Social isolation-induced changes in the hypothalamic-pituitary-adrenal axis in the rat.
2005 Dec
Gonadotropin stimulation of steroid synthesis and metabolism in the Rana pipiens ovarian follicle: sequential changes in endogenous steroids during ovulation, fertilization and cleavage stages.
2006 May
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Fecal steroid metabolites and reproductive monitoring in a female Tsushima leopard cat (Prionailurus bengalensis euptilurus).
2010 Nov
The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain.
2010 Nov 15
Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: mechanisms and reversal by exogenous ACTH.
2010 Oct
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Subjects will receive and intravenous infusion of Allopregnanolone at escalating doses of 2mg, 4mg, and 6mg once weekly over a three week period. The highest dose tolerated without sedation will be held stable for the remaining weekly infusions, for a total of 12 infusions.
Route of Administration: Intravenous
In Vitro Use Guide
GABA-induced current was enhanced by allopregnanolone at concentrations of 0.01 uM and more in guinea-pig adrenal medullary cells.
Name Type Language
BREXANOLONE
INN   USAN  
Official Name English
ALLOPREGNAN-3.ALPHA.-OL-20-ONE [MI]
Common Name English
BREXANOLONE [INN]
Common Name English
ALLOTETRAHYDROPROGESTERONE
Common Name English
BREXANOLONE [WHO-DD]
Common Name English
3.ALPHA.-HYDROXY-5.ALPHA.-PREGNAN-20-ONE
Systematic Name English
PREGNAN-20-ONE, 3-HYDROXY-, (3.ALPHA.,5.ALPHA.)-
Systematic Name English
SGE-102
Code English
(+)-3.ALPHA.-HYDROXY-5.ALPHA.-PREGNAN-20-ONE
Systematic Name English
ALLOPREGNAN-3.ALPHA.-OL-20-ONE
MI  
Common Name English
BREXANOLONE [USAN]
Common Name English
ALLOPREGNANOLONE
Common Name English
SAGE-547
Code English
ZULRESSO
Brand Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 426114
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
FDA ORPHAN DRUG 399013
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
Code System Code Type Description
INN
10446
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
PRIMARY
MERCK INDEX
M1537
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
PRIMARY Merck Index
WIKIPEDIA
ALLOPREGNANOLONE
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
PRIMARY
CAS
516-54-1
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
PRIMARY
PUBCHEM
92786
Created by admin on Mon Oct 21 22:36:31 UTC 2019 , Edited by admin on Mon Oct 21 22:36:31 UTC 2019
PRIMARY