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Hormone · Profile

Allopregnanolone

Brexanolone · Zulresso · 3α,5α-THP

NeurosteroidsApproved
MW
318.5g/mol
Formula
C21H34O2

Allopregnanolone, a neuroactive steroid and a metabolite of progesterone, is primarily produced in the brain and adrenal glands. Researchers primarily study allopregnanolone for its role in mood regulation and its potential implications in postpartum depression (PPD). Key findings from recent studies indicate that brexanolone, a formulation of allopregnanolone, has demonstrated significant reductions in depressive symptoms in women with moderate to severe PPD, with rapid onset of action and sustained effects. Clinical evidence suggests that brexanolone represents a novel therapeutic approach for addressing the unmet needs of women experiencing PPD. Current research continues to explore its broader applications in mood disorders and the underlying mechanisms of its effects on the central nervous system.

Overview

Übersicht

Allopregnanolone, also known as Brexanolone or Zulresso, is an endogenous neurosteroid produced primarily in the central nervous system and peripheral tissues such as the adrenal glands and ovaries. It is a metabolite of progesterone and belongs to the class of neuroactive steroids. Allopregnanolone is synthesized from progesterone via the enzyme 5α-reductase, followed by 3α-hydroxysteroid dehydrogenase action. Researchers have focused on its role in modulating mood and its potential therapeutic applications. Allopregnanolone plays a significant role in modulating GABAergic neurotransmission, which is crucial for maintaining mood stability. It has been extensively studied for its effects on postpartum depression (PPD), where it has shown promise as a treatment option. The compound is also being investigated for its potential effects on other mood disorders, including major depressive disorder and treatment-resistant depression. The primary mechanism of action of allopregnanolone involves positive allosteric modulation of the GABA_A receptors, particularly those containing δ subunits. This modulation enhances inhibitory neurotransmission, leading to anxiolytic and antidepressant effects. The pharmacokinetic properties of allopregnanolone, when administered as Brexanolone, include a rapid onset of action with a half-life of approximately 9 hours following intravenous administration. It undergoes hepatic metabolism and is primarily excreted in the urine. Clinically, Brexanolone is approved by the FDA for the treatment of moderate to severe postpartum depression. It is administered as a continuous intravenous infusion over 60 hours, providing a novel treatment option for women with PPD. The drug's approval marks a significant advancement in the pharmacological management of postpartum depression, offering a rapid and effective therapeutic option.

Chemical profile

Chemische Struktur

Chemical structure of Allopregnanolone
FormelC21H34O2
Molekulargewicht318.5g/mol
CAS-Nummer516-54-1
PubChem CID92786
Mechanism

Wirkmechanismus

Allopregnanolone acts primarily on GABA_A receptors, where it serves as a positive allosteric modulator. This action enhances the inhibitory effects of GABA, leading to increased neuronal inhibition and reduced excitability, which are associated with its anxiolytic and antidepressant effects.

Mechanism

Signalweg

Allopregnanolone acts primarily as a positive allosteric modulator of GABA\(_A\) receptors, particularly those containing the δ subunit, enhancing inhibitory neurotransmission and promoting anxiolytic and antidepressant effects. This modulation leads to increased chloride ion influx, resulting in hyperpolarization of neurons and subsequent attenuation of excitatory neurotransmission, which may influence the HPA axis and contribute to mood stabilization. Although the precise signaling pathways and biological processes involved are still being elucidated, its rapid action in treating postpartum depression highlights its potential as a novel therapeutic agent.

Half-Life & Pharmacokinetics

ENEndogenous

Circulating half-life ~70 minutes

IVIntravenous

~9 hours

POOral

Poor bioavailability due to first-pass metabolism

Intravenous administration is the primary route for therapeutic use due to poor oral bioavailability.

Storage

Temperature

Store at room temperature (15-30C)

Light

Protect from light

Form

Aqueous solution: use within specified period after opening

Notes

Ensure proper handling and storage to maintain stability and efficacy.

Solubility

Löslichkeit

Allopregnanolone is poorly soluble in water but soluble in organic solvents such as ethanol.

Legal Status

🇩🇪DE

Data limited

🇺🇸US

FDA approved for postpartum depression; prescription required.

🇦🇺AU

Data limited

🇬🇧UK

Data limited

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Open Questions

Offene Forschungsfragen

Current evidence is limited regarding the long-term effects of allopregnanolone treatment in diverse populations, particularly in women with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), where its beneficial and harmful effects remain unclear. Further research is needed to conduct larger randomized controlled trials (RCTs) that explore the efficacy and safety of allopregnanolone in these specific populations, as well as to investigate the underlying mechanisms of its action on GABAA receptors in relation to mood disorders. Additionally, studies examining the potential for allopregnanolone to address treatment-resistant depression beyond postpartum depression are warranted to fully understand its therapeutic potential.

68 Research Publications

3,552

Total Citations

15

Human/RCT

4.4

Avg. Influence

2025

Latest

Sort
Filter
#01

Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials.

Meltzer-Brody Samantha, et al. · Lancet (London, England) · 2018

HumanInfluence24.0
466
Researchers observed that brexanolone injection resulted in significant reductions in Hamilton Rating Scale for Depression scores at 60 hours compared to placebo in women with postpartum depression.

Key findings

  1. 01Brexanolone injection led to a greater reduction in depression scores than placebo.
  2. 02The treatment demonstrated quick effects within 60 hours.
  3. 03Adverse events were reported but were generally manageable.
#02

Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial.

HumanInfluence13.0
352
Researchers observed that brexanolone infusion significantly reduced Hamilton Rating Scale for Depression scores in women with severe postpartum depression compared to placebo.
#03

The role of allopregnanolone in depression and anxiety.

ReviewInfluence9.0
278
Researchers observed that reduced levels of allopregnanolone are associated with anxiety and depressive disorders, indicating its potential role in emotional regulation.
#04

Neurosteroids in depression: a review.

ReviewInfluence6.0
216
Researchers observed that allopregnanolone levels normalize following effective treatment with SSRIs in depressed patients, indicating a potential role in the pathophysiology of depression.
#05

Allopregnanolone and mood disorders.

ReviewInfluence7.0
189
Researchers observed that negative mood symptoms in women with PMDD are linked to the paradoxical effects of allopregnanolone on the GABA-A receptor, showing an inverted U-shaped relationship with serum concentrations.
#06

Progesterone - Friend or foe?

Sundström-Poromaa Inger, et al. · Frontiers in neuroendocrinology · 2020

ReviewInfluence4.0
162
Researchers observed that while allopregnanolone is beneficial for postpartum depression treatment, it may also trigger negative symptoms in women with premenstrual syndrome and premenstrual dysphoric disorder.

Key findings

  1. 01Progesterone and its metabolite allopregnanolone have important biological properties and functions.
  2. 02Allopregnanolone may help treat postpartum depression.
  3. 03Progesterone can also trigger negative symptoms in women with PMS and PMDD.
#07

Postpartum Depression: Identification and Treatment in the Clinic Setting.

Kroska Emily B & Stowe Zachary N · Obstetrics and gynecology clinics of North America · 2020

ReviewInfluence5.0
106
Researchers observed that allopregnanolone (Brexanolone) infusion significantly reduces postpartum depression symptoms, as measured by the Edinburgh Postnatal Depression Scale.

Key findings

  1. 01PPD affects up to 15% of women.
  2. 02Risk factors can be identified before delivery.
  3. 03Various effective treatment options are available.
#08

Tolerance to allopregnanolone with focus on the GABA-A receptor.

ReviewInfluence9.0
96
The review indicated that tolerance to allopregnanolone may develop due to variations in GABA-A receptor activity, suggesting implications for its therapeutic use.
#09

Allopregnanolone: An overview on its synthesis and effects.

ReviewInfluence3.0
96
Researchers observed that allopregnanolone, a neuroactive steroid, exhibits sex-dimorphic effects and low bioavailability, suggesting potential therapeutic strategies to increase its levels for neurological disorders.
#10

Allopregnanolone Mediates Affective Switching Through Modulation of Oscillatory States in the Basolateral Amygdala.

AnimalInfluence3.0
93
The study demonstrated that allopregnanolone modulates oscillatory states in the basolateral amygdala, which is linked to its antidepressant effects.

Clinical Trials (14)

Preclinical
Phase I
Phase II
Phase III
Approved

14

Total Trials

746

Total Enrolled

A Study To Assess The Safe-Use Conditions For Administration of ZULRESSO® in a Home Setting

NCT05059600Phase 4COMPLETED
Sponsor

Supernus Pharmaceuticals, Inc.

Enrollment

52

Started

2021

Primary outcome

Percentage of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) Leading to Dose Interruption/Discontinuation

Postpartum Depression

Study on Allopregnanolone and Depression in Perimenopausal Women

NCT05329779Phase 4TERMINATED
Sponsor

Brigham and Women's Hospital

Enrollment

2

Started

2022

Primary outcome

Within-person Change in Score on the Ruminative Responses Scale

Depression

A Study of Brexanolone for Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease 2019 (COVID-19)

NCT04537806Phase 3TERMINATED
Sponsor

Sage Therapeutics

Enrollment

29

Started

2020

Primary outcome

Percentage of Participants Who Are Alive and Free of Respiratory Failure at Day 28

Acute Respiratory Distress SyndromeCOVID-19

Facilitation of Extinction Retention and Reconsolidation Blockade in PTSD

NCT04468360Phase 2RECRUITING
Sponsor

Boston University

Enrollment

256

Started

2022

Primary outcome

Extinction retention in Expt. 1

Post Traumatic Stress Disorder

Allopregnanolone in Chronic Complex Traumatic Brain Injury

NCT04003285Phase 2NOT_YET_RECRUITING
Sponsor

VA Office of Research and Development

Enrollment

132

Started

2026

Primary outcome

Brief Pain Inventory, Short Form (BPI-SF) Change

Traumatic Brain Injury (TBI)

Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

NCT04838301Phase 2RECRUITING
Sponsor

University of Arizona

Enrollment

100

Started

2023

Primary outcome

Hippocampal volume

Alzheimer DementiaLate Onset Alzheimer DiseaseNeurodegenerative Diseases

Facilitation of Extinction Retention and Reconsolidation Blockade by IV Allopregnanolone in PTSD.

NCT07079761Phase 2RECRUITING
Sponsor

Massachusetts General Hospital

Enrollment

96

Started

2025

Primary outcome

Experiment 1: Extinction retention

Post Traumatic Stress Disorder

Allopregnanolone for the Treatment of Traumatic Brain Injury

NCT01673828Phase 2COMPLETED
Sponsor

Michael A. Rogawski, MD, PhD

Enrollment

13

Started

2013

Primary outcome

Extended Glasgow Outcome Scale (GOS-E) Score

Traumatic Brain InjuryPosttraumatic Epilepsy

An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus

NCT05645432Phase 2COMPLETED
Sponsor

Supernus Pharmaceuticals, Inc.

Enrollment

10

Started

2023

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAE)

Tinnitus

Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone

NCT02603926Phase 2COMPLETED
Sponsor

Randi J. Hagerman, MD

Enrollment

6

Started

2015

Primary outcome

California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score

Fragile X-associated Tremor/Ataxia Syndrome

Allopregnanolone for Mild Cognitive Impairment Due to Alzheimer's Disease or Mild AD

NCT02221622Phase 1COMPLETED
Sponsor

University of Southern California

Enrollment

24

Started

2014

Primary outcome

Safety profile: Adverse events

Mild Cognitive ImpairmentAlzheimer Disease

Effect of Allopregnanolone on Stress-induced Craving

NCT04015869Phase 1COMPLETED
Sponsor

Yale University

Enrollment

10

Started

2019

Primary outcome

Alcohol Urge Questionnaire (AUQ) Pre-script

Alcohol Use Disorder

Allopregnanolone as a Regenerative Treatment for Parkinson's Disease

NCT06263010Phase 1COMPLETED
Sponsor

Roberta Brinton

Enrollment

10

Started

2024

Primary outcome

Study completion

Parkinson Disease

Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: Intramuscular Study

NCT03748303Phase 1TERMINATED
Sponsor

University of Arizona

Enrollment

6

Started

2019

Primary outcome

Safety - Adverse events

Alzheimer Dementia

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This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer