Cited by 745Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyEpilepsy research and treatment

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Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes

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Rudolph, Uwe, Knoflach, Frédéric·2011·Nature Reviews Drug Discovery

DOI 10.1038/nrd3502PMC PMC3375401

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Abstract

GABAA (γ-aminobutyric acid, type A) receptors are a family of ligand-gated ion channels that are essential for the regulation of central nervous system function. Benzodiazepines — which non-selectively target GABAA receptors containing the α1, α2, α3 or α5 subunits — have been in clinical use for decades and are still among the most widely prescribed drugs for the treatment of insomnia and anxiety disorders. However, their use is limited by side effects and the risk of drug dependence. In the past decade, the identification of separable key functions of GABAA receptor subtypes suggests that receptor subtype-selective compounds could overcome the limitations of classical benzodiazepines; furthermore, they might be valuable for novel indications such as chronic pain, depression, schizophrenia, cognitive enhancement and stroke.

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Background
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“Figure 3 shows the corresponding isobolograms based on the ED50 values of the drugs alone and combined, with dashed lines representing the theoretical lines of additivity derived from Equation (1).”
BackgroundMethodInfluential
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Authors: Rudolph, U., & Knoflach, F.
Affiliations: Harvard University (US)
F. Hoffmann-La Roche AG (CH)
Corresponding author: Rudolph, Uwe
ORCID: Rudolph, Uwe
Knoflach, Frédéric
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2011-07-29
Volume: 10
Issue: 9
Pages: 685-697
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/nrd3502
PMC: PMC3375401
OpenAlex: W2013775967
Semantic Scholar: bfb4fcd647899053b94eaf5edf1fe9e748076c6b
Cited by: 733
References: 111
Citations by year: 2026: 41 · 2025: 42 · 2024: 35 · 2023: 46 · 2022: 43 · 2021: 55 · 2020: 49 · 2019: 56 · 2018: 51 · 2017: 58 · 2016: 52 · 2015: 45 · 2014: 62 · 2013: 58 · 2012: 38
FWCI: 4.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R21MH087829, R01MH080006, R03MH085149, MH087829, MH085149, MH080006)
National Institute on Drug Abuse (DA027051, DA026578, R03DA026578, R03DA027051)
National Institute of General Medical Sciences (R01GM086448, GM086448)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
Keywords: GABAA receptor, benzodiazepines, GABAA receptor subtypes, ligand-gated ion channels, chronic pain, depression, schizophrenia, cognitive enhancement, stroke, drug addiction
MeSH terms: Analgesics, Animals, Anxiety Disorders, Benzodiazepines, Depressive Disorder, Humans, Hypnotics and Sedatives, Sleep Initiation and Maintenance Disorders, Mutation, Receptors, GABA-A, Schizophrenia, Nootropic Agents, GABA Modulators, Substance-Related Disorders, Stroke

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Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes

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