Allopregnanolone

Allopregnanolone
Clinical data
Trade namesZulresso
Other namesALLO; ALLOP; SAGE-547; SGE-102; 5α-Pregnan-3α-ol-20-one; 5α-Pregnane-3α-ol-20-one;[1][2][3][4][5] 3α-Hydroxy-5α-pregnan-20-one; 3α,5α-Tetrahydroprogesterone; 3α,5α-THP, brexanolone (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa619037
License data
Routes of
administration		Intravenous[6]
Drug classNeurosteroids; Antidepressants
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: <5%[8]
Protein binding>99%[6][8]
MetabolismNon-CYP450 (keto-reduction via aldo-keto reductases (AKR), glucuronidation via glucuronosyltransferases (UGT), sulfation via sulfotransferases (SULT))[6][8]
Elimination half-life9 hours[6][8]
ExcretionFeces: 47%[6][8]
Urine: 42%[6][8]
Identifiers
IUPAC name
  • 1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H34O2
Molar mass318.501 g·mol−1
3D model (JSmol)
SMILES
  • CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC[C@@H]4[C@@]3(CC[C@H](C4)O)C)C
InChI
  • 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
  • Key:AURFZBICLPNKBZ-SYBPFIFISA-N

Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone.[9][10] As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso,[6][11] and used to treat postpartum depression.[10][12][13] It is given by injection into a vein.[10][6]

Side effects of brexanolone may include sedation, sleepiness, dry mouth, hot flashes, and loss of consciousness.[6][10] It is a neurosteroid and acts as a positive allosteric modulator of the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).[6]

Brexanolone was approved for medical use in the United States in 2019.[10][14] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[15] The long administration time, as well as the cost for a one-time treatment, have raised concerns about accessibility for many women.[16]

  1. ^ Krieger NR, Mok WM, Herschkowitz S (September 1990). "5α-Pregnane-3α-ol-20-one Identified as an Active Molecular Species of Steroid Anesthetic in Brain". Anesthesiology. 73. doi:10.1097/00000542-199009001-00702.
  2. ^ Yagen B, Gallili GE, Mateles RI (August 1978). "Progesterone biotransformation by plant cell suspension cultures". Applied and Environmental Microbiology. 36 (2): 213–216. Bibcode:1978ApEnM..36..213Y. doi:10.1128/AEM.36.2.213-216.1978. PMC 291203. PMID 697360.
  3. ^ Meyer HH, Jewgenow K, Hodges JK (February 1997). "Binding activity of 5alpha-reduced gestagens to the progestin receptor from African elephant (Loxodonta africana)". General and Comparative Endocrinology. 105 (2): 164–167. doi:10.1006/gcen.1996.6813. PMID 9038248.
  4. ^ Frye C, Seliga A (May 2002). "Olanzapine and progesterone have dose-dependent and additive effects to enhance lordosis and progestin concentrations of rats". Physiology & Behavior. 76 (1): 151–158. doi:10.1016/s0031-9384(02)00689-3. PMID 12175598. S2CID 38249308.
  5. ^ Mahendroo M, Wilson JD, Richardson JA, Auchus RJ (July 2004). "Steroid 5alpha-reductase 1 promotes 5alpha-androstane-3alpha,17beta-diol synthesis in immature mouse testes by two pathways". Molecular and Cellular Endocrinology. 222 (1–2): 113–120. doi:10.1016/j.mce.2004.04.009. PMID 15249131. S2CID 54297812.
  6. ^ a b c d e f g h i j k "Zulresso- brexanolone injection, solution". DailyMed. 18 November 2019. Retrieved 23 November 2019.
  7. ^ "DEA Schedules Postpartum Depression Treatment Zulresso". Monthly Prescribing Reference. 17 June 2019. Archived from the original on 3 September 2019. Retrieved 24 November 2019.
  8. ^ a b c d e f Cite error: The named reference Scott2019 was invoked but never defined (see the help page).
  9. ^ Reddy DS (2010). "Neurosteroids". Sex Differences in the Human Brain, their Underpinnings and Implications. Progress in Brain Research. Vol. 186. Elsevier. pp. 113–137. doi:10.1016/B978-0-444-53630-3.00008-7. ISBN 9780444536303. PMC 3139029. PMID 21094889.
  10. ^ a b c d e "FDA approves first treatment for post-partum depression". U.S. Food and Drug Administration (FDA) (Press release). 19 March 2019. Archived from the original on 11 October 2019. Retrieved 21 March 2019. This article incorporates text from this source, which is in the public domain.
  11. ^ "ChemIDplus - 516-54-1 - AURFZBICLPNKBZ-SYBPFIFISA-N - Brexanolone [USAN] - Similar structures search, synonyms, formulas, resource links, and other chemical information". NIH Toxnet. Retrieved 26 December 2017.
  12. ^ Frieder A, Fersh M, Hainline R, Deligiannidis KM (March 2019). "Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development". CNS Drugs. 33 (3): 265–282. doi:10.1007/s40263-019-00605-7. PMC 6424603. PMID 30790145.
  13. ^ Wilkinson ST, Sanacora G (February 2019). "A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems". Drug Discovery Today. 24 (2): 606–615. doi:10.1016/j.drudis.2018.11.007. PMC 6397075. PMID 30447328.
  14. ^ "Drug Approval Package: Zulresso". U.S. Food and Drug Administration (FDA). 7 February 2019. Archived from the original on 25 November 2019. Retrieved 6 August 2020.
  15. ^ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Archived from the original on 2 May 2020. Retrieved 15 September 2020.
  16. ^ Chatterjee R (21 March 2019). "New Postpartum Depression Drug Could Be Hard To Access For Moms Most In Need". NPR. Retrieved 22 March 2019.
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