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Palonosetron triggers 5-HT"3 receptor internalization and causes prolonged inhibition of receptor function

Camilo C Rojas, Ajit G AG Thomas, Jesse J Alt, Marigo M Stathis, Jie J Zhang, Edward B EB Rubenstein, Silvia S Sebastiani, Sergio S Cantoreggi, and Barbara S BS Slusher

Eur J Pharmacol 626(2-3):7 (2010) PMID 19836386

Palonosetron is a 5-HT"3 receptor antagonist that has demonstrated superiority in preventing both acute and delayed emesis when compared to older first generation 5-HT"3 receptor antagonists. The objective of this work was to determine if palonosetron exhibits unique molecular interactions with the 5-HT"3 receptor that could provide a scientific rationale for observed clinical efficacy differences. Previously, we showed that palonosetron exhibits allosteric binding and positive cooperativity to the 5-HT"3 receptor in contrast to ondansetron and granisetron which exhibit simple bimolecular binding. The present work shows, through several independent experiments, that palonosetron uniquely triggers 5-HT"3 receptor internalization and induces prolonged inhibition of receptor function. After 24h incubation followed by dissociation conditions, [^3H]palonosetron remained associated with whole cells but not to cell-free membranes (P3 receptor antagonists.

DOI: 10.1016/j.ejphar.2009.10.002
Version: za2963e q8zac q8zb7 q8zc8 q8zde q8zee q8zfa q8zg3

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