Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABA<sub>A</sub> receptors and a homo‐oligomeric GABA receptor from <i>Drosophila melanogaster</i>

Priestley, Caroline M.; Williamson, E. M.; Wafford, Keith A.; Sattelle, David B.

doi:10.1038/sj.bjp.0705542

Cited by 439 publications

(277 citation statements)

References 37 publications

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“…and J.A., unpublished results). Oocyte collection, injection and electrophysiological recordings were carried out as described 35,36 . Two electrode voltage-clamp experiments were performed 1-5 d post-injection.…”

Section: Electrophysiological Recordingmentioning

confidence: 99%

Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila

et al. 2008

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Many lines of evidence indicate that GABA and GABA A receptors make important contributions to human sleep regulation. Pharmacological manipulation of these receptors has differential effects on sleep onset and sleep maintenance insomnia. Here we show that sleep is regulated by GABA in Drosophila and that a mutant GABA A receptor, Rdl A302S , specifically decreases sleep latency. The drug carbamazepine (CBZ) has the opposite effect on sleep; it increases sleep latency as well as decreasing sleep. Behavioral and physiological experiments indicated that Rdl A302S mutant flies are resistant to the effects of CBZ on sleep latency and that mutant RDL A302S channels are resistant to the effects of CBZ on desensitization, respectively. These results suggest that this biophysical property of the channel, specifically channel desensitization, underlies the regulation of sleep latency in flies. These experiments uncouple the regulation of sleep latency from that of sleep duration and suggest that the kinetics of GABA A receptor signaling dictate sleep latency.Insomnia is the most common sleep problem and affects approximately one third of the adult American population 1 . Patients with insomnia are generally subdivided into three categories: sleep onset insomnia, sleep maintenance insomnia and terminal insomnia (early-morning awakening coupled with an inability to return to sleep) 2 . The biological basis for these insomnia classifications remains unknown. Nonetheless, a single class of drugs, agonistic modulators of GABA A receptors, effectively ameliorates these diverse symptoms 2,3 . GABA A receptors are a family of pentameric ligand-gated Cl -channels 4 and are a major source of inhibitory currents throughout the CNS 5,6 . These receptors are also an important target for pharmacologic treatment of many other neurological disorders in addition to sleep 7 .The fruit fly Drosophila melanogaster is an ideal model for dissecting the relationships between molecules and behaviors, as well as between different sleep states 8,9 . As in mammals, it has been shown that the sleep-like state of Drosophila is associated with reduced sensory responsiveness and reduced brain activity 10,11 , and is subject to both circadian and homeostatic regulation 12,13 . Researchers have also identified a number of genes 14,15 , Notably, the mutation that causes the insecticide resistance phenotype (A302S) 20 specifically decreases the rate of RDL desensitization with little or no effect on other channel properties 23 . As a consequence, the mutant receptor has a longer single channel open duration and, therefore, increased channel current, at least under certain conditions (see below). Because of these characteristics, and because this mutation does not have obvious effects on health or viability, we decided to establish the importance of GABAergic transmission to sleep in flies and to examine the effects of the Rdl mutation.Interestingly, flies with this mutant GABA A receptor subunit slept more, primarily because of decreased sleep lat...

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Section: Electrophysiological Recordingmentioning

confidence: 99%

Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila

et al. 2008

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“…Various studies have indicated that monoterpenoids may have several mechanisms of action. Mechanisms that have been reported include: inhibition of acetylcholinesterase (5,6), binding at the GABA receptor (7)(8)(9)(10)(11), binding at the nicotinic acetylcholine receptor (12), the octopamine receptor (13,14), and the tyramine receptor (15). Previous studies have also described quantitative structure-activity relationships (QSARs) to describe the toxicity of monoterpenoids and their interaction at the GABA receptor (11).…”

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confidence: 99%

Quantitative Structure-Activity Relationships (QSARs) of Monoterpenoids at an Expressed American Cockroach Octopamine Receptor

Gross

Kimber

Day

et al. 2013

ACS Symposium Series

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Monoterpenoids are found in essential oils from numerous plant families. Octopamine is a biogenic monoamine found within various invertebrates, including insects. Octopamine exerts its physiological effects through the activation of G-protein-coupled receptors (GPCRs). GPCRs are an under-utilized receptor target in the agrochemical industry. Here we report the expression of an octopamine receptor from the brain of the American cockroach (Periplaneta americana) inSaccharomyces cerevisiae, creating a ligand-independent histidine-auxotrophic assay. The majority of monoterpenoids acted as an inverse agonist in this system. Three QSAR models show that electronic properties are most important for monoterpenoid interaction with this octopamine receptor in this yeast assay.

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“…Their constituents range from terpene hydrocarbons, simple and terpene alcohols, aldehydes, ketones, phenols, lactones, coumarins, to sulfur compounds. Yet the phytochemicals citronellol, linalool, and thymol (for having recognized antimicrobial activities) all stand out (Pereira et al, 2003;Priestley et al, 2003;Botelho et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of cariogenic microorganisms to phytoconstituents

et al. 2018

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This study aimed to evaluate the in vitro antibacterial activity of the phytochemicals thymol, linalool, and citronellol against Streptococcus mutans, Streptococcus salivarius and Streptococcus oralis. Disk diffusion screening on solid medium and measurement of the diameter of the bacterial growth inhibition halos was the technique utilized. The Minimum Inhibitory Concentration (MIC) of the substances was determined using serial substance dilutions and microdilution technique in Brain Heart Infusion culture medium. After incubation for 24 hours in an oven at 37 °C, plate reading was completed and confirmed by visual method using 2,3,5 triphenyl tetrazolium chloride dye. The Minimum Bactericidal Concentration (MBC) was determined from MIC subcultures. Assays were performed in triplicate, and chlorhexidine was used as a positive control. The diameters in mm of the growth inhibition halos ranged between 7.3 and 10.7 for S. mutans, 7.3 and 10.0 for S. oralis, and 8.2 and 9.8 for S. salivarius. The MIC and MBC values obtained converged , ranging from maximum values in the presence of Linalool (1,250.0 mg/mL, 2,500.0 mg/mL and 2,500.0 mg/mL, respectively, for S. mutans, S. oralis, and S. salivarius); and minimum values with Thymol (312.5 μg/ml, 156.2 μg/mL and 156.2 μg/ml, respectively for S. mutans, S. oralis, and S. salivarius). All the tested phytochemicals displayed antibacterial activity, thus representing substances with potential applications in preventing tooth decay.Keywords: preventive dentistry, dental caries, citronellol, linalool, thymol. Susceptibilidade de microrganismos cariogênicos a fitoconstituintes ResumoEste estudo objetivou avaliar a atividade antibacteriana in vitro dos fitoquímicos timol, linalol e citronelol sobre Streptococcus mutans, Streptococcus salivaris e Streptococcus oralis. Utilizou-se a técnica de discos de difusão em meio sólido e medição do diâmetro dos halos de inibição. A concentração inibitória mínima (CIM) das substâncias foi determinada utilizando diluições em série das substâncias e técnica de microdiluição em meio de cultura de Brain Heart Infusion. Após incubação durante 24 horas em estufa a 37 °C, a leitura da placa foi confirmada pelo método visual usando o corante 2,3,5 trifenil cloreto de tetrazólio. A concentração bactericida mínima (CBM) foi determinada a partir de subculturas de MIC. Os ensaios foram realizados em triplicata, e clorexidina foi usada como um controle positivo. Os diâmetros dos halos de inibição do crescimento variaram entre 7,3 e 10,7 por S. mutans, 7,3 e 10,0 por S. oralis, e 8,2 e 9,8 para S. salivaris. Os valores de CIM e CBM obtidos variaram de valores máximos na presença de linalol (1.250,0 mg/mL, 2.500.0 mg/mL e 2.500.0 mg/mL, respectivamente, para o S. mutans, S oralis e S. salivaris); a valores mínimos com timol (312,5 μg/ml, 156,2 μg/mL e 156,2 μg

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Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABA_A receptors and a homo‐oligomeric GABA receptor from Drosophila melanogaster

Cited by 439 publications

References 37 publications

Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila

Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila

Quantitative Structure-Activity Relationships (QSARs) of Monoterpenoids at an Expressed American Cockroach Octopamine Receptor

Susceptibility of cariogenic microorganisms to phytoconstituents

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Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABAA receptors and a homo‐oligomeric GABA receptor from Drosophila melanogaster

Cited by 439 publications

References 37 publications

Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila

Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila

Quantitative Structure-Activity Relationships (QSARs) of Monoterpenoids at an Expressed American Cockroach Octopamine Receptor

Susceptibility of cariogenic microorganisms to phytoconstituents

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Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABA_A receptors and a homo‐oligomeric GABA receptor from Drosophila melanogaster