BREXANOLONE

US Previously Marketed

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 Search

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

Molecular Formula	C21H34O2
Molecular Weight	318.4935
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25126056 | https://www.ncbi.nlm.nih.gov/pubmed/21094889 | http://www.medscape.com/viewarticle/843607 | http://adisinsight.springer.com/drugs/800039944

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

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; agonist GABA site 13 Target ID: CHEMBL2109244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23978486 \| https://www.ncbi.nlm.nih.gov/pubmed/25799373	Positive Allosteric Modulator 186		75.5 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Status epilepticus 12 Sources: http://www.medscape.com/viewarticle/843607	Primary	Phase III 665	Unknown Approved Use Unknown
Postnatal depression 1 Sources: http://adisinsight.springer.com/drugs/800039944 https://www.ncbi.nlm.nih.gov/pubmed/24215796	Primary	Phase III 665	Unknown Approved Use Unknown
Essential tremor 6 Sources: http://adisinsight.springer.com/drugs/800039944	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
52 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	60 μg/kg/h 1 times / day steady-state, intravenous dose: 60 μg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
79 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	90 μg/kg/h 1 times / day steady-state, intravenous dose: 90 μg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
71.8 pmol/mL CLINICAL TRIAL https://link.springer.com/article/10.1007/s00213-005-0148-7	0.09 mg/kg 3 times / day multiple, intravenous dose: 0.09 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	BREXANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
14.53 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
42.05 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
60.07 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	6 mg single, intravenous dose: 6 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
25.85 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	2 mg 1 times / day steady-state, intravenous dose: 2 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
38.69 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	4 mg 1 times / day steady-state, intravenous dose: 4 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
58.47 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	6 mg 1 times / day steady-state, intravenous dose: 6 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
8897 ng × min/L CLINICAL TRIAL https://link.springer.com/article/10.1007/s00213-005-0148-7	0.09 mg/kg 3 times / day multiple, intravenous dose: 0.09 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	BREXANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
7.7 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
24.35 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
37 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	6 mg single, intravenous dose: 6 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
13.21 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	2 mg 1 times / day steady-state, intravenous dose: 2 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
25.06 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	4 mg 1 times / day steady-state, intravenous dose: 4 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
34.26 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/33344752/	6 mg 1 times / day steady-state, intravenous dose: 6 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	60 μg/kg/h 1 times / day steady-state, intravenous dose: 60 μg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	90 μg/kg/h 1 times / day steady-state, intravenous dose: 90 μg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered:	ALLOPREGNANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
261 min CLINICAL TRIAL https://link.springer.com/article/10.1007/s00213-005-0148-7	0.09 mg/kg 3 times / day multiple, intravenous dose: 0.09 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	BREXANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	60 μg/kg/h 1 times / day steady-state, intravenous dose: 60 μg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ALLOPREGNANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	90 μg/kg/h 1 times / day steady-state, intravenous dose: 90 μg/kg/h route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ALLOPREGNANOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 ug/kg/day 3 times / 60 hours multiple, intravenous Recommended Dose: 60 ug/kg/day, 3 times / 60 hours Route: intravenous Route: multiple Dose: 60 ug/kg/day, 3 times / 60 hours Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf https://pubmed.ncbi.nlm.nih.gov/30177236/	unhealthy, 18 to 45 years Health Status: unhealthy Age Group: 18 to 45 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf https://pubmed.ncbi.nlm.nih.gov/30177236/	Other AEs: Dizziness, Somnolence... Other AEs: Dizziness (grade 1, 13%) Somnolence (grade 1, 21%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf https://pubmed.ncbi.nlm.nih.gov/30177236/
60 ug/kg/day 3 times / 60 hours multiple, intravenous Recommended Dose: 60 ug/kg/day, 3 times / 60 hours Route: intravenous Route: multiple Dose: 60 ug/kg/day, 3 times / 60 hours Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	unhealthy, 18 to 45 years Health Status: unhealthy Age Group: 18 to 45 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	Other AEs: Diarrhea, Dry mouth... Other AEs: Diarrhea (3%) Dry mouth (11%) Oropharyngeal pain (3%) Loss of consciousness (5%) Flush hot (5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf
75 ug/kg/day multiple, intravenous Recommended Dose: 75 ug/kg/day Route: intravenous Route: multiple Dose: 75 ug/kg/day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	unhealthy, 18 to 45 years Health Status: unhealthy Age Group: 18 to 45 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	DLT: Loss of consciousness, Syncope... Disc. AE: Loss of consciousness, Vertigo... Dose limiting toxicities: Loss of consciousness Syncope Somnolence Dizziness Fatigue Infusion related reaction Change in blood pressure AEs leading to discontinuation/dose reduction: Loss of consciousness Vertigo Syncope Presyncope Infusion site pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf
90 ug/kg/day 5 times / 60 hours multiple, intravenous Recommended Dose: 90 ug/kg/day, 5 times / 60 hours Route: intravenous Route: multiple Dose: 90 ug/kg/day, 5 times / 60 hours Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	unhealthy, 18 to 45 years Health Status: unhealthy Age Group: 18 to 45 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf	Other AEs: Tachycardia, Diarrhea... Other AEs: Tachycardia (2%) Diarrhea (2%) Dry mouth (3%) Dyspepsia (2%) Oropharyngeal pain (2%) Dizziness (12%) Loss of consciousness (3%) Somnolence (13%) Flush hot (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf
90 ug/kg/day 5 times / 60 hours multiple, intravenous Recommended Dose: 90 ug/kg/day, 5 times / 60 hours Route: intravenous Route: multiple Dose: 90 ug/kg/day, 5 times / 60 hours Sources: https://pubmed.ncbi.nlm.nih.gov/28619476/	unhealthy, 20 to 40 years Health Status: unhealthy Age Group: 20 to 40 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/28619476/	Other AEs: Dizziness, Nausea... Other AEs: Dizziness (grade 1, 20%) Nausea (grade 1, 10%) Rash (grade 1, 10%) Somnolence (grade 1-2, 20%) Dizziness postural (grade 1, 10%) Dry mouth (grade 1, 10%) Hot flush (grade 1, 10%) Pyrexia (grade 1, 10%) Sedation (grade 1, 10%) Sinus tachycardia (grade 2, 10%) Vertigo (grade 1, 10%) Sources: https://pubmed.ncbi.nlm.nih.gov/28619476/
270 ug/kg/day 1 times / day single, intravenous Highest studied dose Dose: 270 ug/kg/day, 1 times / day Route: intravenous Route: single Dose: 270 ug/kg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000OtherR.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000OtherR.pdf	Other AEs: Somnolence, Feeling of relaxation... Other AEs: Somnolence (93.7%) Feeling of relaxation (9.4%) Feeling abnormal (6.3%) Psychomotor retardation (3.1%) Euphoric mood (12.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000OtherR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438 inducer 440	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav1.2 58 BCRP 910 P-gp 1741 MRP2 499 BSEP 550 MRP3 246 MRP4 290 MATE1 415 MATE2 267 OAT1 725 OAT3 747 OATP1B1 1079 OATP1B3 961 OCT1 620 OCT2 779 UGT2B1 1 CYP1A2 2153 CYP2C19 2057 CYP2C8 1057 CYP2B6 926 UGT1A1 246 UGT1A3 89 UGT1A4 98 UGT1A6 136 UGT1A9 148 UGT2B7 197 UGT2B15 84	CYP2C8 810 CYP2C19 1119 UGT2B7 456 UGT2B17 237 BCRP 697 P-gp 2052 BSEP 63 OATP1B1 503 OATP1B3 435 OCT1 393	CYP2B6 669 CYP1A2 832 CYP3A 142 UGT1A9 9

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 17 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 49 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
CYP3A 317	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MRP3 326	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MRP4 345	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A3 99	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A4 100	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A6 171	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A9 155	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A9 155	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT2B15 84	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT2B7 210	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	yes [IC50 0.41 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes [IC50 0.41 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes [Inhibition 2 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	yes
MRP3 326	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
MRP3 326	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
MRP3 326	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
MRP4 345	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
MRP4 345	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
MRP4 345	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
UGT2B1 22	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	yes

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
UGT2B17 237	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50169	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50169
ChemicalBook	CB5418550	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5418550
eMolecules	531093	https://www.emolecules.com/cgi-bin/more?vid=531093
MolPort	MolPort-003-892-356	https://www.molport.com/shop/molecule-link/MolPort-003-892-356
ZINC	ZINC000004081043	http://zinc15.docking.org/substances/ZINC000004081043

PubMed

Title	Date	PubMed
The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain.	2010-11-15	20665558
Fecal steroid metabolites and reproductive monitoring in a female Tsushima leopard cat (Prionailurus bengalensis euptilurus).	2010-11	20615533
Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: mechanisms and reversal by exogenous ACTH.	2010-10	20633208
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007-01	17003167
Gonadotropin stimulation of steroid synthesis and metabolism in the Rana pipiens ovarian follicle: sequential changes in endogenous steroids during ovulation, fertilization and cleavage stages.	2006-05	16678716
Social isolation-induced changes in the hypothalamic-pituitary-adrenal axis in the rat.	2005-12	16423714
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.	2002-09	12367616
The influence of subunit composition on the interaction of neurosteroids with GABA(A) receptors.	2002-09	12367610
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.	2001-12	11739473
Profiling neurosteroids in cerebrospinal fluids and plasma by gas chromatography/electron capture negative chemical ionization mass spectrometry.	2000-01-15	10625505
Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.	1998-10-13	9770465
Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine.	1998-03-17	9501247

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:55:29 GMT 2025` Edited by `admin` on `Mon Mar 31 21:55:29 GMT 2025`
Record UNII	S39XZ5QV8Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALLOPREGNAN-3.ALPHA.-OL-20-ONE

Preferred Name

English

BREXANOLONE

Official Name

English

ALLOPREGNAN-3.ALPHA.-OL-20-ONE [MI]

Common Name

English

brexanolone [INN]

Common Name

English

Brexanolone [WHO-DD]

Common Name

English

ALLOTETRAHYDROPROGESTERONE

Common Name

English

3?-Hydroxy-5?-pregnan-20-one

Systematic Name

English

BREXANOLONE [ORANGE BOOK]

Common 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

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