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• W1596247996 abstract "BACKGROUND AND PURPOSE Betahistine, the main histamine drug prescribed to treat vestibular disorders, is a histamine H 3 receptor antagonist. Here, we explored the potential for modulation of the most recently cloned histamine receptor (H 4 receptor) to influence vestibular system function, using a selective H 4 receptor antagonist JNJ 7777120 and the derivate compound JNJ 10191584. EXPERIMENTAL APPROACH RT‐PCR was used to assess the presence of H 4 receptors in rat primary vestibular neurons. In vitro electrophysiological recordings and in vivo behavioural approaches using specific antagonists were employed to examine the effect of H 4 receptor modulation in the rat vestibular system. KEY RESULTS The transcripts of H 4 and H 3 receptors were present in rat vestibular ganglia. Application of betahistine inhibited the evoked action potential firing starting at micromolar range, accompanied by subsequent strong neuronal depolarization at higher concentrations. Conversely, reversible inhibitory effects elicited by JNJ 10191584 and JNJ 7777120 began in the nanomolar range, without inducing neuronal depolarization. This effect was reversed by application of the selective H 4 receptor agonist 4‐methylhistamine. Thioperamide, a H 3 /H 4 receptor antagonist, exerted effects similar to those of H 3 and H 4 receptor antagonists, namely inhibition of firing at nanomolar range and membrane depolarization above 100 µM. H 4 receptor antagonists significantly alleviated the vestibular deficits induced in rats, while neither betahistine nor thioperamide had significant effects. CONCLUSIONS AND IMPLICATIONS H 4 receptor antagonists have a pronounced inhibitory effect on vestibular neuron activity. This result highlights the potential role of H 4 receptors as pharmacological targets for the treatment of vestibular disorders." @default.
• W1596247996 created "2016-06-24" @default.
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• W1596247996 date "2012-09-25" @default.
• W1596247996 modified "2023-10-18" @default.
• W1596247996 title "Histamine H₄receptor antagonists as potent modulators of mammalian vestibular primary neuron excitability" @default.
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• W1596247996 doi "https://doi.org/10.1111/j.1476-5381.2012.02049.x" @default.
• W1596247996 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3575788" @default.
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