General
Preferred name
BREXANOLONE
Synonyms
ELTANOLONE ()
3¦Á,5¦Á-THP ()
SAGE-547 ()
3??,5??-THP ()
ALLOPREGNANOLONE ()
Zulresso ()
(3?,5?)-3-Hydroxy-pregnan-20-one ()
5α-pregnan-3α-ol-20-one ()
Allopregnan-3.alpha.-ol-20-one ()
SGE-102 ()
Allotetrahydroprogesterone ()
Allopregnanolone ()
P&D ID
PD013675
CAS
516-54-1
128-20-1
Tags
natural product
drug
available
Drug Status
investigational
approved
Drug indication
Depression
Status epilepticus seizure
Essential tremor or related tremors
Postpartum depression
Max Phase
Phase 4
First approval
2019
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
This steroidal compound behaves as a neuroactive agent with anti-depressant activity in mood disorders . Pharmacologically it is a positive allosteric modulator of GABAA receptors.
(GtoPdb)
PHARMACODYNAMICS
Brexanolone potentiated GABA-mediated currents from recombinant human GABA(a) receptors in mammalian cells expressing α1β2γ2 receptor subunits, α4β3δ receptor subunits, and α6β3δ receptor subunits [FDA Label][F4063, F4072].; ; Moreover, it was determined during a Phase 1 randomized, placebo and positive-controlled, double-blind, three-period crossover thorough QT study in 30 healthy adult subjects that brexanolone use did not prolong the QT interval to any clinically relevant extent when administered at 1.9-times the exposure occurring at the highest recommended infusion rate (90 mcg/kg/hour) [FDA Label][F4063, F4072].
ABSORPTION
It has been determined that brexanolone has a low oral bioavailability of approximately <5% in adults, which suggests infant exposure would also be expected to be low [FDA Label].
METABOLISM
Brexanolone is extensively metabolized by non-cytochrome (CYP) based pathways by way of three main routes - keto-reduction (via aldo-keto reductases), glucuronidation (via UDP-glucuronosyltransferases), and sulfation (via sulfotransferases) [FDA Label]. Three predominant circulating metabolites result from such metabolic pathways and they are all pharmacologically inactive and ultimately do not contribute to the overall efficacy of the medication [FDA Label].
HALF-LIFE
The terminal half-life observed for brexanolone is approximately 9 hours [FDA Label].
PHARMACODYNAMICS
Brexanolone potentiated GABA-mediated currents from recombinant human GABA(a) receptors in mammalian cells expressing α1β2γ2 receptor subunits, α4β3δ receptor subunits, and α6β3δ receptor subunits [FDA Label][F4063, F4072]. Moreover, it was determined during a Phase 1 randomized, placebo and positive-controlled, double-blind, three-period crossover thorough QT study in 30 healthy adult subjects that brexanolone use did not prolong the QT interval to any clinically relevant extent when administered at 1.9-times the exposure occurring at the highest recommended infusion rate (90 mcg/kg/hour) [FDA Label][F4063, F4072].
ROE
Following the administration of radiolabeled brexanolone, it was observed that 47% of the administrated dose was recovered largely as metabolites in the feces and 42% in urine, where less than 1% as recovered as unchanged brexanolone [FDA Label].
INDICATION
Brexanolone is a synthetic neuroactive steroid gamma-aminobutyric acid A (GABA(a)) receptor positive modulator indicated for the treatment of postpartum depression (PPD) in adult women [FDA Label][A176080, A176083, F4063, F4066, F4072].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
3
Compound Sets
20
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugMAP
DrugMAP Approved Drugs
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
NPC Screening Collection
Other bioactive compounds
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
54
Molecular Weight
318.26
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
1
Rotatable Bonds
1
Ring Count
4
Aromatic Ring Count
0
cLogP
4.6
TPSA
37.3
Fraction CSP3
0.95
Chiral centers
8.0
Largest ring
6.0
QED
0.77
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Membrane Transporter/Ion Channel
Target
GABA
MOA
GABA Receptor
Biosynthetic Origin
Terpenoid (Steroid)
Therapeutic Indication
Antidepressant
Therapeutic Class
CNS & PNS
Source data
