Type A γ-aminobutyric acid (GABAA) receptor subunits and benzodiazepine binding

Significance to clinical syndromes and their treatment

Timothy Andrew Davies Smith

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

GABAA receptor subunits and benzodiazepine binding: Significance to clinical disorders and their treatment

Gamma (gamma)-aminobutyric acid (GABA) acting via GABAA receptors is the brain's major inhibitory neurotransmitter system and exerts a crucial role in regulating brain excitability. A number of drugs interact with binding sites on GABAA receptors, and these include benzodiazepines, anticonvulsants, anaesthetics and neurosteroids (e.g. the progesterone metabolite pregnalone). GABAA receptors comprise five subunits (19 are known currently), and are classified into three major groups (alpha, beta and gamma) and several minor ones. The subunit make-up of a receptor, particularly its alpha-subunit content, determines its pharmacological characteristics. Thus, receptors that include an alpha1 subunit have a benzodiazepine (BZ) type I (BZ[I]) pharmacology and bind zolpidem and CL218,872 with high affinity, whilst receptors with alpha2, alpha3 or alpha5 subunits have a BZ type II (BZ[II]) pharmacology and bind these drugs with low affinity. In contrast to receptors that contain alpha4 and alpha6 subunits, which are diazepam-insensitive, both BZ(I) and -(II) bind diazepam and other benzodiazepines. The ligand selectivity of receptor subunits assists in their characterisation. Using immunochemical and ligand-binding techniques, the subunit composition of GABAA receptors has been shown to exhibit a degree of brain regional specificity. GABAA receptors are of great clinical significance in several disorders, including epilepsy, anxiety and alcoholism. In addition to treating epilepsy with drugs that target GABAA and BZ binding sites, epileptic lesions can be localised presurgically using radiolabelled BZ ligands. BZs are used commonly to treat anxiety, and studies suggest that BZ antagonists and inverse agonists (which induce the opposite effect to agonists at receptors) may be useful in alcohol rehabilitation.
Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalBritish Journal of Biomedical Science
Volume58
Issue number2
Publication statusPublished - 1 Jan 2001

Fingerprint

Aminobutyrates
GABA-A Receptors
Benzodiazepines
Brain
Therapeutics
Pharmacology
Diazepam
Ligands
Neurotransmitter Agents
Epilepsy
Anxiety
Binding Sites
Pharmaceutical Preparations
Metabolites
Patient rehabilitation
Anticonvulsants
gamma-Aminobutyric Acid
Alcoholism
Progesterone
Anesthetics

Keywords

  • Alcoholism
  • Anxiety
  • Benzodiazepines
  • Epilepsy
  • Receptors, GABA-A

Cite this

Type A γ-aminobutyric acid (GABAA) receptor subunits and benzodiazepine binding : Significance to clinical syndromes and their treatment . / Smith, Timothy Andrew Davies.

In: British Journal of Biomedical Science, Vol. 58, No. 2, 01.01.2001, p. 111-121.

Research output: Contribution to journalArticle

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