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• W2130900903 abstract "6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1<i>H</i>-3-benzazepin-7-yl)oxy]-<i>N</i>-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) is a novel histamine H₃ receptor antagonist with high affinity for human (p<i>K</i>_i = 9.59 –9.90) and rat (p<i>K</i>_i = 8.51–9.17) H₃ receptors. GSK189254 is >10,000-fold selective for human H₃ receptors versus other targets tested, and it exhibited potent functional antagonism (p<i>A</i>₂ = 9.06 versus agonist-induced changes in cAMP) and inverse agonism [pIC₅₀ = 8.20 versus basal guanosine 5′-<i>O</i>-(3-[³⁵S]thio)triphosphate binding] at the human recombinant H₃ receptor. In vitro autoradiography demonstrated specific [³H]GSK189254 binding in rat and human brain areas, including cortex and hippocampus. In addition, dense H₃ binding was detected in medial temporal cortex samples from severe cases of Alzheimer9s disease, suggesting for the first time that H₃ receptors are preserved in late-stage disease. After oral administration, GSK189254 inhibited cortical ex vivo <i>R</i>-(–)-α-methyl[imidazole-2,5(<i>n</i>)-³H]histamine dihydrochloride ([³H]<i>R</i>-α-methylhistamine) binding (ED₅₀ = 0.17 mg/kg) and increased c-Fos immunoreactivity in prefrontal and somatosensory cortex (3 mg/kg). Microdialysis studies demonstrated that GSK189254 (0.3–3 mg/kg p.o.) increased the release of acetylcholine, noradrenaline, and dopamine in the anterior cingulate cortex and acetylcholine in the dorsal hippocampus. Functional antagonism of central H₃ receptors was demonstrated by blockade of <i>R</i>-α-methylhistamine-induced dipsogenia in rats (ID₅₀ = 0.03 mg/kg p.o.). GSK189254 significantly improved performance of rats in diverse cognition paradigms, including passive avoidance (1 and 3 mg/kg p.o.), water maze (1 and 3 mg/kg p.o.), object recognition (0.3 and 1 mg/kg p.o.), and attentional set shift (1 mg/kg p.o.). These data suggest that GSK189254 may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer9s disease and other cognitive disorders." @default.
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• W2130900903 date "2007-02-27" @default.
• W2130900903 modified "2023-10-03" @default.
• W2130900903 title "GSK189254, a Novel H₃Receptor Antagonist That Binds to Histamine H₃Receptors in Alzheimer's Disease Brain and Improves Cognitive Performance in Preclinical Models" @default.
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• W2130900903 cites W2004525253 @default.
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• W2130900903 cites W2016079923 @default.
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• W2130900903 cites W2046432652 @default.
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• W2130900903 doi "https://doi.org/10.1124/jpet.107.120311" @default.
• W2130900903 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17327487" @default.
• W2130900903 hasPublicationYear "2007" @default.
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