Abstract
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.
Highlights
There have recently been two important advances relating to the improvement of anti-emetic treatment given to patients undergoing anti-cancer therapies
Metoclopramide 2 x 0.65, 2 x 1.25 and 2 x 2.5mg kg- 1 i.v. reduced the emesis evoked by cis-platin, whereas domperidone 2 x 1.0 and 2 x 2.5mg kg-1 i.v. had no effects (Table II)
Our experiments with ferrets and domperidone confirm the inability of dopamine antagonists to inhibit emesis evoked by cis-platin, even though a similar dose of domperidone prevented apomorphine-evoked emesis
Summary
There have recently been two important advances relating to the improvement of anti-emetic treatment given to patients undergoing anti-cancer therapies. It was found that, unlike conventional doses of metoclopramide (Maxolon; Beecham Pharmaceuticals) which antagonise dopamine receptors and stimulate gastric motility, high doses of the drug greatly reduced cis-platin-evoked emesis (Gralla et al, 1981). Even high doses of the dopamine antagonists, domperidone (Motilium; Janssen Pharmaceuticals) or alizapride, have little or no ability to prevent cis-platininduced emesis (Tonato et al, 1985; Saller & Hellenbrecht, 1985). Mechanisms other than dopamine receptor antagonism have been implicated in this antiemetic action of metoclopramide (McRitchie et al, 1984)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
