Neurosteroids: endogenous regulators of the GABAA receptor
Abstract
GABA(A) (gamma-aminobutyric acid type A) receptors mediate most of the 'fast' synaptic inhibition in the mammalian brain and are targeted by many clinically important drugs. Certain naturally occurring pregnane steroids can potently and specifically enhance GABA(A) receptor function in a nongenomic (direct) manner, and consequently have anxiolytic, analgesic, anticonvulsant, sedative, hypnotic and anaesthetic properties. These steroids not only act as remote endocrine messengers, but also can be synthesized in the brain, where they modify neuronal activity locally by modulating GABA(A) receptor function. Such 'neurosteroids' can influence mood and behaviour in various physiological and pathophysiological situations, and might contribute to the behavioural effects of psychoactive drugs.
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Allopregnanolone is a potent allosteric modulator of GABAA, while 5α-pregnane-3α,20α-diol is less neuroactive.
“Allopregnanolone is a potent allosteric modulator of GABAA, while 5α-pregnane-3α,20α-diol is less neuroactive”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [42]
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- Authors
- Belelli, D., & Lambert, J. J.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Lambert, Jeremy J.
- Venue
- Nature reviews. Neuroscience
- Published
- 2005-06-15
- Volume
- 6
- Issue
- 7
- Pages
- 565-575
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2070510853
- Semantic Scholar
- 1e15686792dd96994a0bd1337b50f1e4448b7965
- Cited by
- 1,159
- References
- 123
- Citations by year
- 2026: 32 · 2025: 40 · 2024: 45 · 2023: 51 · 2022: 49 · 2021: 52 · 2020: 53 · 2019: 49 · 2018: 54 · 2017: 43 · 2016: 57 · 2015: 57 · 2014: 71 · 2013: 64 · 2012: 55
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- neurosteroids, GABAA receptor, pregnane steroids, non-genomic steroid action, synaptic inhibition, anxiolytic effects, anticonvulsant activity, anesthesia, psychoactive substances
- MeSH terms
- Animals, Brain, Humans, Models, Biological, Neural Inhibition, Synaptic Transmission, Pregnanes, Receptors, GABA-A, Antipsychotic Agents, Mood Disorders
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