ArticleAnesthesiology2017
Competitive Antagonism of Anesthetic Action at the γ-Aminobutyric Acid Type A Receptor by a Novel Etomidate Analog with Low Intrinsic Efficacy.
Article in Anesthesiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Antagonism of propofol anesthesia by alkyl-fluorobenzene derivatives.Scientific reports · 2024Article
- Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.Anesthesiology · 2024Article
- Antagonism of Propofol Anesthesia by Alkyl-fluorobenzene Derivatives.Research square · 2024Article
- Selective actions of benzodiazepines at the transmembrane anaesthetic binding sites of the GABABritish journal of pharmacology · 2021Article
- Competitive Antagonism of Etomidate Action by Diazepam: In Vitro GABAA Receptor and In Vivo Zebrafish Studies.Anesthesiology · 2020Article
- Etomidate and Etomidate Analog Binding and Positive Modulation of γ-Aminobutyric Acid Type A Receptors: Evidence for a State-dependent Cutoff Effect.Anesthesiology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe authors characterized the γ-aminobutyric acid type A receptor pharmacology of the novel etomidate analog naphthalene-etomidate, a potential lead compound for the development of anesthetic-selective competitive antagonists.
methodsThe positive modulatory potencies and efficacies of etomidate and naphthalene-etomidate were defined in oocyte-expressed α1β3γ2L γ-aminobutyric acid type A receptors using voltage clamp electrophysiology. Using the same technique, the ability of naphthalene-etomidate to reduce currents evoked by γ-aminobutyric acid alone or γ-aminobutyric acid potentiated by etomidate, propofol, pentobarbital, and diazepam was quantified. The binding affinity of naphthalene-etomidate to the transmembrane anesthetic binding sites of the γ-aminobutyric acid type A receptor was determined from its ability to inhibit receptor photoaffinity labeling by the site-selective photolabels [H]azi-etomidate and R-[H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid.
resultsIn contrast to etomidate, naphthalene-etomidate only weakly potentiated γ-aminobutyric acid-evoked currents and induced little direct activation even at a near-saturating aqueous concentration. It inhibited labeling of γ-aminobutyric acid type A receptors by [H]azi-etomidate and R-[H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid with similar half-maximal inhibitory concentrations of 48 μM (95% CI, 28 to 81 μM) and 33 μM (95% CI, 20 to 54 μM). It also reduced the positive modulatory actions of anesthetics (propofol > etomidate ~ pentobarbital) but not those of γ-aminobutyric acid or diazepam. At 300 μM, naphthalene-etomidate increased the half-maximal potentiating propofol concentration from 6.0 μM (95% CI, 4.4 to 8.0 μM) to 36 μM (95% CI, 17 to 78 μM) without affecting the maximal response obtained at high propofol concentrations.
conclusionsNaphthalene-etomidate is a very low-efficacy etomidate analog that exhibits the pharmacology of an anesthetic competitive antagonist at the γ-aminobutyric acid type A receptor.
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