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• W2079077377 abstract "Changes in various histamine (HA) H3 receptor-mediated responses and H3 receptor binding in brain were investigated in mice receiving single or repeated administration of ciproxifan, a potent brain-penetrating and selective H3 receptor antagonist. Blockade of the H3 autoreceptor was nearly as effective in enhancing levels of tele-methylhistamine (t-MeHA), a major HA metabolite, in brain areas when ciproxifan was administered once either at 7 a.m. or 8 p.m., in spite of the large differences of basal levels at these two phases of the circadian cycle. Blockade after a single ciproxifan administration was, however, followed by a transient decrease in striatal t-MeHA levels, possibly reflecting rapid development of autoreceptor hypersensitivity. Following a 5-day administration of ciproxifan and a 2-day drug-free period, basal t-MeHA levels were significantly decreased (approximately -20%) in three brain areas, and the ED50 values of the drug to enhance t-MeHA levels were increased by 5-15 times without significant change in maximal response, indicating that H3 autoreceptor hypersensitivity had developed. However, in synaptosomes from the cerebral cortex of these animals, the H3 receptor-mediated inhibition of K+-induced [3H]HA release was not significantly modified. Subchronic administration of ciproxifan for 10 days also resulted in an increased binding of [125I]iodoproxyfan to the H3 receptor of striatal and hypothalamic membranes by 40-54%. Hypersensitivity at H3 somatodendritic autoreceptors and at heteroreceptors attributable to an increased number of HA binding sites could account for the various changes observed in this study." @default.
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• W2079077377 date "2001-12-25" @default.
• W2079077377 modified "2023-10-03" @default.
• W2079077377 title "Changes in Histamine H3 Receptor Responsiveness in Mouse Brain" @default.
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• W2079077377 doi "https://doi.org/10.1046/j.1471-4159.2000.0740339.x" @default.
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