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Pharmacological and anti-emetic properties of ondansetron
M B Tyers1, K T Bunce, P P Humphrey
1Glaxo Group Research Limited, Ware, Hertfordshire, U.K.
Abstract:
Three main types of 5-HT (serotonin) receptor have been recognised. The 5-HT3 receptor is located on neuronal tissues in the peripheral and central nervous systems. Ondansetron is a highly selective and potent antagonist for this receptor type. The severe nausea and vomiting caused by cytotoxic agents and radiotherapy can be reduced by metoclopramide treatment, but extrapyramidal side effects are common due to antagonism of dopamine receptors. Ondansetron has been found to significantly delay the onset of emesis, and reduce the number of retches and vomits in ferrets receiving cisplatin, cyclophosphamide, or radiation, at much lower doses than metoclopramide and without the associated side effects. Experiments to define the site of action of ondansetron suggest that at least part of its antiemetic action is in the area postrema, though a peripheral site of action in the upper gastrointestinal tract is also a possibility.
Insights
Ondansetron effectively reduces chemotherapy-induced nausea and vomiting by selectively blocking serotonin 5-HT3 receptors. This antiemetic offers a safer alternative to metoclopramide, with fewer side effects.
Area of Science:
- Pharmacology
- Neuroscience
- Gastroenterology
Background:
- Serotonin 5-HT3 receptors are implicated in nausea and vomiting.
- Current treatments like metoclopramide have significant side effects due to dopamine antagonism.
- Ondansetron is a selective 5-HT3 receptor antagonist.
Purpose of the Study:
- To evaluate the efficacy and safety of ondansetron as an antiemetic.
- To compare ondansetron's antiemetic properties with metoclopramide.
- To investigate the site of action for ondansetron's antiemetic effects.
Main Methods:
- Administration of ondansetron and metoclopramide to ferrets receiving emetogenic stimuli (cisplatin, cyclophosphamide, radiation).
- Assessment of emesis onset, retches, and vomits.
- Experiments to determine the central and peripheral sites of action.
Main Results:
- Ondansetron significantly delayed emesis and reduced vomiting and retching at lower doses than metoclopramide.
- Ondansetron did not cause the extrapyramidal side effects associated with metoclopramide.
- Evidence suggests ondansetron acts in the area postrema and potentially peripherally.
Conclusions:
- Ondansetron is a potent and selective antiemetic for managing chemotherapy- and radiotherapy-induced nausea and vomiting.
- Ondansetron offers a superior safety profile compared to metoclopramide.
- The antiemetic action of ondansetron involves both central (area postrema) and possibly peripheral mechanisms.