ArticleEuropean journal of pharmacology2010
The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes.
Article in European journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00005536 (Genetic Analysis of Human Hypertensive End Stage Renal Disease), which is not on this map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic Analysis of Human Hypertensive End Stage Renal Disease (H-ESRD)
Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
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- Subregion-Specific Impacts of Genetic Loss of Diazepam Binding Inhibitor on Synaptic Inhibition in the Murine Hippocampus.Neuroscience · 2018Article
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- The Benefits of Genetic Addiction Risk Score (GARSInternational journal of genomics and data mining · 2018Article
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- Optimization of substituted imidazobenzodiazepines as novel asthma treatments.European journal of medicinal chemistry · 2017Article
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- Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface.Scientific reports · 2016Article
- Development of GABAA Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments.Molecular pharmaceutics · 2016Article
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- Negative modulation of α₅ GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion.Journal of psychopharmacology (Oxford, England) · 2015Article
- Endozepines.Advances in pharmacology (San Diego, Calif.) · 2015Review
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5 authors at 1 institution in 1 country.
Funding
Abstract
Benzodiazepine site agonists or inverse agonists enhance or reduce gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of neurons, respectively. Recently, it was demonstrated that the point mutation gamma 2F77I causes a drastic change in the affinity of a variety of benzodiazepine agonists or inverse agonists in receptor binding studies. Here we investigated the potency and efficacy of 10 benzodiazepine site ligands from 6 structural classes in wild-type and gamma 2F77I point mutated recombinant GABA(A) receptors composed of alpha 1 beta 3 gamma 2, alpha 2 beta 3 gamma 2, alpha 3 beta 3 gamma 2, alpha 4 beta 3 gamma 2, alpha 5 beta 3 gamma 2, and alpha 6 beta 3 gamma 2 subunits. Results indicate that the effects of the benzodiazepine site ligands zolpidem, zopiclone, Cl218872, L-655,708 and DMCM were nearly completely eliminated in all mutated receptors up to a 1 microM concentration. The effects of bretazenil, Ro15-1788 or abecarnil were eliminated in some, but not all mutated receptors, suggesting that the gamma 2F77I mutation differentially influences the actions of these ligands in different receptor subtypes. In addition, this point mutation also influences the efficacy of diazepam for enhancing GABA-induced chloride flux, suggesting that the amino acid residue gamma 2F77 might also be involved in the transduction of the effect of benzodiazepines from binding to gating. The application of these drugs in a novel mouse model is discussed.
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