ArticleBritish journal of pharmacology2005
Anxiogenic properties of an inverse agonist selective for alpha3 subunit-containing GABA A receptors.
Article in British journal of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04592536 (A Randomized, Double-blind, Placebo- and Active Comparator-controlled, Crossover Trial to Examine the Effect of Multiple Doses of CVL-865 on Panic Symptoms Induced by Carbon Dioxide Inhalation in Healthy Subject), which is not on this map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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.
A Randomized, Double-blind, Placebo- and Active Comparator-controlled, Crossover Trial to Examine the Effect of Multiple Doses of CVL-865 on Panic Symptoms Induced by Carbon Dioxide Inhalation in Healthy Subject
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Model-based meta-analysis of the effects of non-selective and α1-selective GABAA receptor agonists in healthy volunteers.European journal of clinical pharmacology · 2015Pooled it
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- GABACellular and molecular neurobiology · 2026Review
- Age-dependent increases in dorsal hippocampal postsynaptic α5GABA-a receptors may be lost in a rat model of Alzheimer's disease.Scientific reports · 2025Article
- Genetic and genomic analysis of reproduction traits in holstein cattle using SNP chip data and imputed sequence level genotypes.BMC genomics · 2024Article
- Role of α1-GABAJournal of psychopharmacology (Oxford, England) · 2024Article
- Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation.Frontiers in behavioral neuroscience · 2023Article
- Effects of α5 GABACNS neuroscience & therapeutics · 2022Article
- A multi-dosing regimen to enhance the spatial memory of normal rats with α5-containing GABAPsychopharmacology · 2021Article
- Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAFrontiers in neuroscience · 2020Review
- Molecular docking analysis of α2-containing GABAA receptors with benzimidazoles derivatives.Bioinformation · 2020Article
- Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety.Acta pharmacologica Sinica · 2019Review
- Valium without dependence? Individual GABANeuropsychiatric disease and treatment · 2018Review
- A Pharmacogenetic 'Restriction-of-Function' Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by α5-Containing GABAA Receptors in Mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Anxiety Evokes Hypofrontality and Disrupts Rule-Relevant Encoding by Dorsomedial Prefrontal Cortex Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Assessment of subunit-dependent direct gating and allosteric modulatory effects of carisoprodol at GABA(A) receptors.Neuropharmacology · 2015Article
- The effects of repeated zolpidem treatment on tolerance, withdrawal-like symptoms, and GABAA receptor mRNAs profile expression in mice: comparison with diazepam.Psychopharmacology · 2014Article
- Long-term behavioral programming induced by peripuberty stress in rats is accompanied by GABAergic-related alterations in the Amygdala.PloS one · 2014Article
- An anxiogenic drug, FG 7142, induced an increase in mRNA of Btg2 and Adamts1 in the hippocampus of adult mice.Behavioral and brain functions : BBF · 2012Article
- Voluntary exercise offers anxiolytic potential and amplifies galanin gene expression in the locus coeruleus of the rat.Behavioural brain research · 2012Article
Corrections and comments
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11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Alpha3IA (6-(4-pyridyl)-5-(4-methoxyphenyl)-3-carbomethoxy-1-methyl-1H-pyridin-2-one) is a pyridone with higher binding and functional affinity and greater inverse agonist efficacy for GABA(A) receptors containing an alpha3 rather than an alpha1, alpha2 or alpha5 subunit. If doses are selected that minimise the occupancy at these latter subtypes, then the in vivo effects of alpha3IA are most probably mediated by the alpha3 subtype. Alpha3IA has good CNS penetration in rats and mice as measured using a [(3)H]Ro 15-1788 in vivo binding assay. At doses in rats that produce relatively low levels of occupancy (12%) in the cerebellum (i.e. alpha1-containing receptors), alpha3IA (30 mg kg(-1) i.p.), like the nonselective partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG 7142), not only caused behavioural disruption in an operant, chain-pulling assay but was also anxiogenic in the elevated plus maze, an anxiogenic-like effect that could be blocked with the benzodiazepine antagonist Ro 15-1788 (flumazenil). Neurochemically, alpha3IA (30 mg kg(-1) i.p.) as well as FG 7142 (15 mg kg(-1) i.p.) increased the concentration of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in rat medial prefrontal cortex by 74 and 68%, respectively, relative to vehicle-treated animals, a response that mimicked that seen following immobilisation stress. Taken together, these data demonstrate that an inverse agonist selective for GABA(A) receptors containing an alpha3 subunit is anxiogenic, and suggest that since alpha3-containing GABA(A) receptors play a role in anxiety, then agonists selective for this subtype should be anxiolytic.
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