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- W1983107136 abstract "The effect of T-2328 {2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride}, a novel tachykinin NK1–receptor antagonist, was examined on cisplatin-induced emesis in ferrets. Cisplatin induced acute emesis in 24 h and delayed emesis during 24 and 72 h, respectively. Ondansetron, a 5-HT3 antagonist, almost completely blocked the acute emesis and transiently reduced the delayed emesis. In contrast, T-2328 elicited long-lasting anti-emetic effects on both acute and delayed phases by a single intravenous administration. Suppression of delayed emesis was not due to elimination of the acute phase because the delayed emesis was also suppressed by administration after the onset of delayed emesis. Persistent blockade of NK1 receptors in the brain was demonstrated by inhibition of the NK1 agonist–induced foot tapping response for over 24 h. An appreciable amount of T-2328 was present in the brain 32 and 72 h after the injection. The NK1 agonist–induced contractions of isolated ileum in guinea pigs was antagonized with IC50 values of 1.4 nM in an insurmountable manner. It is likely that T-2328 exerts the long-lasting anti-emetic effect by not only long-term presence in the brain but also its insurmountable inhibition of NK1 receptors." @default.
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- W1983107136 date "2008-01-01" @default.
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- W1983107136 title "Long-Lasting Anti-emetic Effect of T-2328, a Novel NK1 Antagonist" @default.
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- W1983107136 doi "https://doi.org/10.1254/jphs.08027fp" @default.
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