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Hormone · Profile

Allopregnanolone

Brexanolone · Zulresso · 3α,5α-THP

NeurosteroidsApproved
MW
318.5g/mol
Formula
C21H34O2

Allopregnanolone, a neuroactive steroid derived from progesterone, is primarily synthesized 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 shown significant efficacy in reducing depressive symptoms in women with moderate to severe PPD, with rapid onset of action and a durable response. Clinical evidence suggests that this novel treatment represents a significant advancement in addressing the unmet needs of women experiencing PPD. Current research continues to explore the broader applications of allopregnanolone in mood disorders and its mechanisms of action within the central nervous system.

Overview

Übersicht

Allopregnanolone, also known as Brexanolone or Zulresso, is a neuroactive steroid that is both endogenously produced and synthetically available. It is a metabolite of progesterone and is primarily synthesized in the central nervous system, adrenal glands, and reproductive tissues. As a member of the neurosteroid class, it plays a significant role in modulating neuronal excitability through its action on neurotransmitter receptors. Researchers have found that allopregnanolone is involved in various physiological processes, particularly those related to mood regulation and stress response. It has been extensively studied for its potential therapeutic effects in postpartum depression (PPD) and other mood disorders. The compound acts as a positive allosteric modulator of the gamma-aminobutyric acid type A (GABAA) receptors, enhancing the inhibitory effects of GABA and contributing to its anxiolytic and antidepressant properties. This mechanism is crucial for its rapid onset of action in alleviating depressive symptoms. Pharmacokinetically, allopregnanolone has a relatively short half-life when administered intravenously, necessitating continuous infusion for therapeutic efficacy. It undergoes hepatic metabolism and is primarily excreted in urine. Clinically, brexanolone has been approved by the FDA for the treatment of moderate to severe postpartum depression, marking a significant advancement in addressing this condition. It is administered as an intravenous infusion over 60 hours in a controlled medical setting. Regulatory approval has been granted in the USA, with ongoing evaluations in other regions.

Chemical profile

Chemische Struktur

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

Wirkmechanismus

Allopregnanolone acts primarily on GABAA receptors, functioning as a positive allosteric modulator. This interaction enhances the inhibitory action of GABA, leading to increased neuronal inhibition and a subsequent reduction in anxiety and depressive symptoms.

Mechanism

Signalweg

Allopregnanolone, a positive allosteric modulator of GABAA receptors, enhances GABAergic neurotransmission, leading to increased inhibitory signaling in the central nervous system. This modulation primarily affects δ-containing GABAA receptors, which are implicated in the regulation of mood and anxiety, potentially influencing the HPA axis and neuroplasticity. While the exact mechanisms remain to be fully elucidated, the rapid antidepressant effects observed in postpartum depression suggest significant involvement of GABAergic pathways in its therapeutic action.

Half-Life & Pharmacokinetics

ENEndogenous

Circulating half-life ~70 minutes

IVIntravenous

~9 hours

POOral

Poor bioavailability due to first-pass metabolism

Intravenous administration is required for therapeutic effect due to poor oral bioavailability.

Storage

Temperature

Refrigerate at 2-8C

Light

Protect from light

Form

Aqueous solution: use within specified period after opening

Notes

Ensure solution is clear and free from particulates before use.

Solubility

Löslichkeit

Allopregnanolone is poorly soluble in water but soluble in ethanol and other organic solvents.

Legal Status

🇩🇪DE

Data limited

🇺🇸US

FDA approved for postpartum depression; prescription required; not scheduled by DEA.

🇦🇺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 and safety of allopregnanolone treatments, particularly in diverse populations beyond postpartum women, such as those with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Further research is needed to explore the potential adverse effects of allopregnanolone in these populations and to clarify the mechanisms underlying its dual role as both a therapeutic agent and a potential trigger for negative mood symptoms. Additionally, larger randomized controlled trials (RCTs) are necessary to establish the efficacy of allopregnanolone in treatment-resistant depression and to assess its long-term impact on mental health outcomes.

69 Research Publications

3,787

Total Citations

17

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
467
Researchers observed significant reductions in Hamilton Rating Scale for Depression scores in women with postpartum depression receiving brexanolone compared to placebo.

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
354
The study demonstrated that brexanolone infusion resulted in a significant reduction in depression scores in women with severe postpartum depression compared to placebo.
#03

The role of allopregnanolone in depression and anxiety.

ReviewInfluence10.0
278
The review suggested that reduced allopregnanolone levels may contribute to anxiety and depression, highlighting its potential as a therapeutic target in these disorders.
#04

Neurosteroids in depression: a review.

ReviewInfluence6.0
217
The review found that decreased levels of allopregnanolone in depressed patients normalize with effective treatment, suggesting its potential role in the pathophysiology of depression.
#05

Progesterone and allopregnanolone in the central nervous system: response to injury and implication for neuroprotection.

ReviewInfluence4.0
207
The review highlighted that increased local biosynthesis of allopregnanolone may serve as an endogenous neuroprotective mechanism in response to nervous system injuries.
#06

Allopregnanolone and mood disorders.

ReviewInfluence8.0
190
Researchers observed that negative mood symptoms in women with PMDD are linked to allopregnanolone serum concentrations, exhibiting an inverted U-shaped relationship with GABA-A receptor modulation.
#07

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, 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.
#08

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
108
Researchers observed that brexanolone infusion demonstrated benefits in managing postpartum depression, highlighting its potential as a treatment option.

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.
#09

Allopregnanolone: An overview on its synthesis and effects.

ReviewInfluence3.0
97
Researchers observed that allopregnanolone's synthesis and effects are influenced by physiological and pathological conditions, with implications for gender-specific treatment strategies.
#10

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.

Clinical Trials (14)

Preclinical
Phase I
Phase II
Phase III
Approved

14

Total Trials

501

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

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 2ACTIVE_NOT_RECRUITING
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

Pharmacokinetic Study for IV Allopregnanolone

NCT04468360Phase 2TERMINATED
Sponsor

Boston University

Enrollment

11

Started

2022

Primary outcome

Clinician Assessed Sedation Levels for Each Participant

Pharmacokinetic StudyPost Traumatic Stress Disorder

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