ArticleBritish journal of pharmacology2008
Characterization of (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one as a positive allosteric modulator of GABAB receptors.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 102 citations in OpenAlex.
- Multisession Anodal Transcranial Direct Current Stimulation Enhances Adult Hippocampal Neurogenesis and Context Discrimination in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Allosteric modulation of G protein-coupled receptor signaling.Frontiers in endocrinology · 2023Review
- Keeping the Balance: GABABrain sciences · 2022Review
- GABACurrent topics in behavioral neurosciences · 2022Article
- GABACurrent topics in behavioral neurosciences · 2022Review
- GABACurrent topics in behavioral neurosciences · 2022Article
- Article
- Molecular mechanisms of metabotropic GABAScience advances · 2021Review
- Rational approaches for the design of various GABA modulators and their clinical progression.Molecular diversity · 2021Review
- Cryo-EM structures of inactive and active GABACell research · 2020Article
- Potential of GABACNS drugs · 2019Review
- Structural biology of GABANeuropharmacology · 2018Review
- An Allosteric Potentiator of the Dopamine D1 Receptor Increases Locomotor Activity in Human D1 Knock-In Mice without Causing Stereotypy or Tachyphylaxis.The Journal of pharmacology and experimental therapeutics · 2017Article
- Computational Advances for the Development of Allosteric Modulators and Bitopic Ligands in G Protein-Coupled Receptors.The AAPS journal · 2015Review
- Activation of the γ-Aminobutyric Acid Type B (GABA(B)) Receptor by Agonists and Positive Allosteric Modulators.Journal of medicinal chemistry · 2015Review
- GABAB receptor upregulates fragile X mental retardation protein expression in neurons.Scientific reports · 2015Article
- Inhibition of alcohol self-administration by positive allosteric modulators of the GABAB receptor in rats: lack of tolerance and potentiation of baclofen.Psychopharmacology · 2015Article
- Evaluation of peripheral versus central effects of GABA(B) receptor activation using a novel, positive allosteric modulator of the GABA(B) receptor ADX71943, a pharmacological tool compound with a fully peripheral activity profile.British journal of pharmacology · 2014Article
- Discovery of a Negative Allosteric Modulator of GABAB Receptors.ACS medicinal chemistry letters · 2014Article
- Positive allosteric modulation of GABAB receptors ameliorates sensorimotor gating in rodent models.CNS neuroscience & therapeutics · 2014Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAs baclofen is active in patients with anxiety disorders, GABAB receptors have been implicated in the modulation of anxiety. To avoid the side effects of baclofen, allosteric enhancers of GABAB receptors have been studied to provide an alternative therapeutic avenue for modulation of GABAB receptors. The aim of this study was to characterize derivatives of (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) as enhancers of GABAB receptors. EXPERIMENTAL APPROACH: Enhancing properties of rac-BHFF were assessed in the Chinese hamster ovary (CHO)-Galpha16-hGABA(B1a,2a) cells by Fluorometric Imaging Plate Reader and GTPgamma[35S]-binding assays, and in rat hippocampal slices by population spike (PS) recordings. In vivo activities of rac-BHFF were assessed using the loss of righting reflex (LRR) and stress-induced hyperthermia (SIH) models. KEY
resultsIn GTPgamma[35S]-binding assays, 0.3 microM rac-BHFF or its pure enantiomer (+)-BHFF shifted the GABA concentration-response curve to the left, an effect that resulted in a large increase in both GABA potency (by 15.3- and 87.3-fold) and efficacy (149% and 181%), respectively. In hippocampal slices, rac-BHFF enhanced baclofen-induced inhibition of PS of CA1 pyramidal cells. In an in vivo mechanism-based model in mice, rac-BHFF increased dose-dependently the LRR induced by baclofen with a minimum effective dose of 3 mg kg(-1) p.o. rac-BHFF (100 mg kg(-1) p.o.) tested alone had no effect on LRR nor on spontaneous locomotor activity, but exhibited anxiolytic-like activity in the SIH model in mice. CONCLUSIONS AND IMPLICATIONS: rac-BHFF derivatives may serve as valuable pharmacological tools to elucidate the pathophysiological roles played by GABAB receptors in the central and peripheral nervous systems.
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