SELECTIVITY OF 5-HT3 RECEPTOR ANTAGONISTS AND ANTIEMETIC MECHANISMS OF ACTION

被引:72
作者
FREEMAN, AJ
CUNNINGHAM, KT
TYERS, MB
机构
[1] Glaxo Group Research, Greenford UB7 7UE, Greenford Road
关键词
EMESIS; CHEMOTHERAPY; GRANISETRON; 5-HT3; ONDANSETRON; TROPISETRON;
D O I
10.1097/00001813-199204000-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
5-HT3 receptor antagonists, ondansetron, granisetron and tropisetron are highly specific for the 5-HT3 receptor and have a selectivity ratio of approximately 1000:1 compared with affinities for other receptors. Other 5-HT3 receptor antagonists, largely those having a benzamide structure, are non-selective. These include metoclopramide, renzapride and zacopride which stimulate gastric motility via activation of 5-HT4 receptors; metoclopramide is also a potent dopamine receptor antagonist. Selective 5-HT3 receptor antagonists are a major advance in the treatment of chemotherapy- and radiotherapy-induced emesis in cancer patients. These agents inhibit emesis by blocking 5-HT3 receptors on vagal afferent nerve terminals in the gastrointestinal mucosa and on terminals on the same vagal nerves in the vomiting system. Inhibition of acute emesis appears to be produced by blocking the initiation of the emetic reflex induced via 5-HT3 receptors and by 5-HT released from enterochromaffin cells in the small intestine, as well as by blocking 5-HT3 receptors in the hindbrain vomiting system.
引用
收藏
页码:79 / 85
页数:7
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