Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis
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Published version
Embargoed until: 5555-01-01
Reason: Publisher version
Embargoed until: 5555-01-01
Reason: Publisher version
Pagination
159 - 162 (4)
Publisher
Journal
British Journal of Cancer
ISSN
1532-1827
Metadata
Show full item recordAbstract
The involvement of 5-hydroxytryptamine (5-HT) 5-HT3 receptors in the mechanisms of severe
emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic
compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant
and dopamine antagonist at conventional doses, a 5-HT3 receptor antagonist at higher doses) and BRL 24924
(a potent gastric motility stimulant and a 5-HT3 receptor antagonist). Domperidone or metoclopramide
prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not
prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924
greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis
evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a
fundamental role for 5-HT3 receptors in the mechanisms mediating severely emetogenic cancer treatment
therapies.