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• W2005339341 endingPage "37" @default.
• W2005339341 startingPage "26" @default.
• W2005339341 abstract "Nausea and vomiting are major side effects of chemotherapy and one key reason for non-compliance with cancer treatment. The introduction of 5-HT3 receptor antagonists in the 1990s was a major advance in the prevention of acute emesis, and highlighted the critical role of serotonin in the emetic response. The next major advance in the treatment of chemotherapy induced nausea and vomiting (CINV) occurred in 2003 with the introduction of aprepitant, a tachykinin 1 (NK1) receptor antagonist. Aprepitant not only reduced acute emesis but also helped in the reduction of delayed emesis. Also in 2003, palonosetron, a second generation 5-HT3 receptor antagonist became available. Unlike the first generation 5-HT3 receptor antagonists, palonosetron demonstrated efficacy in preventing both acute and delayed emesis. This review focuses on the mechanism of action of 5-HT3 and NK1 receptor antagonists in acute and delayed CINV prevention. We discuss first, the medicinal chemistry that led to the discovery of these antagonists to underline their common structural features. Second, we discuss their performance in the clinic and what it tells us about the emetic response. Finally, we present recent mechanistic studies that help provide a rationale for efficacy differences between palonosetron and other 5-HT3 receptor antagonists in the clinic. In vitro and in vivo experiments have shown that palonosetron can inhibit substance P-mediated responses, presumably through its unique interactions with the 5-HT3 receptor. The crossroads of acute and delayed emesis seem to include interactions among the 5-HT3 and NK1 receptor signaling pathways and inhibitions of these interactions could lead to improved treatment of CINV." @default.
• W2005339341 created "2016-06-24" @default.
• W2005339341 creator A5017074842 @default.
• W2005339341 creator A5023686004 @default.
• W2005339341 creator A5050473857 @default.
• W2005339341 creator A5078466007 @default.
• W2005339341 date "2014-01-01" @default.
• W2005339341 modified "2023-10-12" @default.
• W2005339341 title "Molecular mechanisms of 5-HT3 and NK1 receptor antagonists in prevention of emesis" @default.
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