BREXANOLONE

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

[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC[C@@]4([H])C[C@H](O)CC[C@]34C

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 179		75.5 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Status epilepticus 12 Sources: http://www.medscape.com/viewarticle/843607	Primary	Phase III 656	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 656	Unknown Approved Use Unknown
Essential tremor 6 Sources: http://adisinsight.springer.com/drugs/800039944	Primary	Phase II 1132	Unknown Approved Use 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 n = 38 Health Status: unhealthy Condition: postpartum depression Age Group: 18 to 45 years Sex: F Population Size: 38 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 n = 38 Health Status: unhealthy Condition: postpartum depression Age Group: 18 to 45 years Sex: F Population Size: 38 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 (mean) 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 n = 140 Health Status: unhealthy Condition: postpartum depression Age Group: 18 to 45 years Sex: F Population Size: 140 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 n = 102 Health Status: unhealthy Condition: postpartum depression Age Group: 18 to 45 years Sex: F Population Size: 102 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 n = 10 Health Status: unhealthy Condition: postpartum depression Age Group: 20 to 40 years Sex: F Population Size: 10 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 n = 32 Health Status: healthy Age Group: adult Population Size: 32 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 1737 inhibitor 1587	substrate 1037 inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav1.2 45 BCRP 699 P-gp 1461 MRP2 383 BSEP 402 MRP3 157 MRP4 204 MATE1 306 MATE2 263 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 UGT2B1 1 CYP1A2 1524 CYP2C19 1478 CYP2C8 911 CYP2B6 810 UGT1A1 204 UGT1A3 84 UGT1A4 77 UGT1A6 108 UGT1A9 116 UGT2B7 146 UGT2B15 64	CYP2C8 693 CYP2C19 991 UGT2B7 389 UGT2B17 213 BCRP 561 P-gp 1537 BSEP 52 OATP1B1 406 OATP1B3 350 OCT1 327	CYP2B6 547 CYP1A2 701 CYP3A 129 UGT1A9 9

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 17 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 49 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no [IC50 >100 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	no
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A3 93	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A4 80	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A6 141	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A9 121	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT1A9 121	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT2B15 64	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	yes [IC50 0.41 uM]
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes [IC50 0.41 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes [Inhibition 2 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=44 Page: 44.0	yes
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M133 1
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M136 1
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	yes	M137 1
UGT2B1 22	inhibitor 3277 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 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=43 Page: 43.0	unlikely
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
UGT2B17 213	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0	yes
UGT2B7 389	substrate 3367 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 49	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211371Orig1s000MultidisciplineR.pdf#page=40 Page: 40.0
hERG 1647	inhibitor 1626 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
MolPort	MolPort-003-892-356	https://www.molport.com/shop/molecule-link/MolPort-003-892-356
ZINC	ZINC000004081043	http://zinc15.docking.org/substances/ZINC000004081043
eMolecules	531093	https://www.emolecules.com/cgi-bin/more?vid=531093

PubMed

Title	Date	PubMed
Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.	1998 Oct 13	9770465
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	11739473
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	12367616
The influence of subunit composition on the interaction of neurosteroids with GABA(A) receptors.	2002 Sep	12367610
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain.	2010 Nov 15	20665558

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 `Sat Dec 16 08:10:21 UTC 2023` Edited by `admin` on `Sat Dec 16 08:10:21 UTC 2023`
Record UNII	S39XZ5QV8Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

3α-Hydroxy-5α-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

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

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