Ondansetron: A revolutionary antiemetic drug

Today We’ll introduce anti nausea medication. Ondansetron is a revolutionary antiemetic drug used to treat nausea and vomiting. Let’s know it more

What Is Ondansetron

1. Structural features:

White or off-white crystalline powder, odorless, bitter taste, readily soluble in methanol, slightly soluble in water, and sparingly soluble in acetone. Containing carbazole and imidazole rings, it is a highly selective 5-HT3 receptor antagonist.

2. Synthesis mechanism and metabolism:

Ondansetron can be produced by reacting 2-bromoaniline with 1,3-cyclohexanedione, followed by dehydrogenation and cyclization to generate a tetrahydrocarbazole derivative. This derivative then reacts with dimethylamine and paraformaldehyde, followed by iodomethane, and finally with 2-methyl-1H-imidazole in dimethylformamide. Ondansetron is primarily metabolize in the liver to a sulfate conjugate, with no active metabolites.

3. Functional characteristics:

Antiemetics are use to prevent or treat nausea and vomiting caused by chemotherapy, radiotherapy, or surgery. Their mechanism of action is to block peripheral and central 5-HT3 receptors, inhibiting the excitation of vagal afferent nerves.

Research and Development Background

The development of ondansetron was driven by the need to address the clinical challenge of nausea and vomiting following chemotherapy, radiotherapy, or surgery. Nausea and vomiting not only affect patients’ quality of life but can also lead to complications, such as dehydration, electrolyte imbalance, and malnutrition, and even impact patient adherence to and tolerance of treatment. At the time, existing antiemetic drugs, such as dopamine receptor antagonists and glucocorticoids , were not ideally effective and had numerous adverse reactions.

Therefore, a new type of antiemetic drug was urgently needed to effectively prevent and treat nausea and vomiting caused by chemotherapy, radiotherapy, or surgery, while also being highly safe and having few side effects. Its development journey is a story of hard-won success, a tale of a backup plan finally taking center stage. Ondansetron was initially develop by GlaxoSmithKline ( GSK ) in 1984 as an antipsychotic drug in clinical trials.

However, the trials revealed that ondansetron had no significant effect on psychosis. But have a good effect on controlling nausea and vomiting. Therefore, GSK decided to develop ondansetron as an antiemetic. After years of effort, ondansetron was finally approved by the US “FDA in 1990,”, becoming the first 5-HT3 receptor antagonist antiemetic. Since then, ondansetron has been widely used worldwide for the prevention and treatment of nausea and vomiting caused by chemotherapy, radiotherapy, or surgery, and is considered a revolutionary drug.

The transformation of ondansetron from a failed antipsychotic to a successful antiemetic is inseparable from scientists’ in-depth research into the mechanism of action of serotonin (5-HT) in nausea and vomiting. As early as the 1970s, it was discovered that serotonin could induce nausea and vomiting, and that this was related to nausea and vomiting induced by chemotherapy drugs. Later, it was found that multiple types of serotonin receptors exist in the gastrointestinal tract and central nervous system, among which the 5-HT3 receptor is closely related to nausea and vomiting.

Therefore, scientists began searching for compounds that could block 5-HT3 receptors to achieve an antiemetic effect. Ondansetron is such a compound; it can highly selectively antagonize peripheral and central 5-HT3 receptors, thereby inhibiting vagal afferent nerve excitation and reducing the nausea and vomiting reflex. Ondansetron not only pioneered the use of 5-HT3 receptor antagonist antiemetics but also provided reference and inspiration for the development of other similar drugs.

Medicinal chemistry

Ondansetron is an organic compound with the chemical formula C18H19N3O. It is a white or off-white crystalline powder, odorless, with a bitter taste. It is readily soluble in methanol, slightly soluble in water, and sparingly soluble in acetone. Containing carbazole and imidazole rings, it is a highly selective 5-HT3 receptor antagonist. It can be synthesized artificially through a multi-step reaction or extracted from certain plants. Its hydrochloride or acetate salts are commonly used and have antiemetic effects.

Pharmacology

Ondansetron is an antiemetic primarily use to prevent or treat nausea and vomiting induced by chemotherapy, radiotherapy, or surgery. Its mechanism of action involves blocking peripheral and central 5-HT3 receptors, inhibiting vagal afferent nerve excitation. It has no significant effect on the central nervous system and does not affect gastrointestinal motility. Combining it with other antiemetics, such as dopamine receptor antagonists or glucocorticoids, can enhance its antiemetic effect.

Pharmacokinetics

Ondansetron is rapidly absorb by the gastrointestinal tract, subcutaneous tissue, and mucous membranes. Oral bioavailability is approximately 60%, with peak plasma concentrations reached after intravenous injection. Ondansetron is primarily metabolized in the liver to sulfate conjugates; there are no active metabolites, and approximately 86% is excreted in the urine and 14% in the feces. The plasma half-life is approximately 3–4 hours, regardless of dose. It can cross the blood-brain barrier and the placental barrier.

Drug dosage form

Ondansetron is available in various dosage forms, including injection, oral tablets, oral solutions, and oral disintegrating tablets. The injection solution is 2ml:4mg; the oral tablets are 4mg or 8mg; the oral solution is 5ml:4mg; and the oral disintegrating tablets are 4mg or 8mg.

Adverse drug reactions and contraindications

The main adverse reactions of ondansetron include headache , and occasionally constipation, diarrhea, fever, rash, and abnormal liver function. It is contraindicate in patients with known hypersensitivity to ondansetron. Pregnant women, breastfeeding mothers, and children should use it with caution. Contraindications for ondansetron include hypersensitivity to ondansetron or other 5-HT3 receptor antagonists; concomitant use with certain arrhythmia-inducing drugs such as quinolones and macrolides may increase the risk of QT interval prolongation and ventricular arrhythmias, therefore, concomitant use should be avoide.

Clinical application

Ondansetron is primarily used to prevent or treat nausea and vomiting induced by chemotherapy, radiotherapy, or surgery. It is often use in combination with other antiemetics such as dopamine receptor antagonists or corticosteroids to enhance the antiemetic effect and reduce adverse reactions. Ondansetron is also included in the World Health Organization‘s list of essential medicines as a basic antiemetic.

Drug Interactions

Ondansetron’s effects can be enhance when use in combination with other 5-HT3 receptor antagonists such as granicetec and toremirone. However, its use with certain arrhythmia medications such as quinolones and macrolides may increase the risk of QT interval prolongation and ventricular arrhythmias, therefore, such combination should be avoided. Concomitant use with certain liver enzyme inhibitors such as cimetidine and erythromycin may increase plasma ondansetron concentrations, therefore, dose adjustment is necessary. Concomitant use with certain liver enzyme inducers such as phenytoin sodium and rifampin may decrease plasma ondansetron concentrations, therefore, dose adjustment is necessary.

Key related points (examination and application)

Ondansetron is an antiemetic primarily used to prevent or treat nausea and vomiting induced by chemotherapy, radiotherapy, or surgery. Its mechanism of action involves blocking peripheral and central 5-HT3 receptors , inhibiting vagal nerve excitation. Ondansetron is mainly metabolize in the liver to a sulfate conjugate, with no active metabolites. The main adverse reaction of ondansetron is headache ; occasionally, constipation, diarrhea, and fever may occur. It is contraindicated in patients with known hypersensitivity to ondansetron.

❓ Frequently Asked Questions About Ondansetron

1. What is Ondansetron used for?

Ondansetron is primarily use to prevent and treat nausea and vomiting caused by chemotherapy, radiotherapy, or surgery. It works by blocking 5-HT3 receptors in the brain and gut, which are responsible for triggering the vomiting reflex.

2. How does Ondansetron work in the body?

Ondansetron acts as a highly selective 5-HT3 receptor antagonist, blocking both central and peripheral receptors. This prevents the stimulation of vagal afferent nerves, which helps reduce nausea and vomiting.

3. What are the common dosage forms of Ondansetron?

Ondansetron is available in multiple forms:

• Injection: 2ml:4mg
• Oral tablets: 4mg or 8mg
• Oral solution: 5ml:4mg
• Oral disintegrating tablets: 4mg or 8mg

4. Are there any side effects of Ondansetron?

Yes. Common side effects include:

• Headache
• Constipation or diarrhea
• Fever or rash
• Liver function abnormalities (rare) Patients with known hypersensitivity to Ondansetron should avoid its use.

5. Can Ondansetron be used during pregnancy or breastfeeding?

Ondansetron should be used with caution during pregnancy and breastfeeding. Always consult a healthcare provider before use in these cases.

6. Does Ondansetron interact with other medications?

Yes. Ondansetron may interact with:

• Arrhythmia-inducing drugs (e.g., quinolones, macrolides)
• Liver enzyme inhibitors (e.g., cimetidine, erythromycin)
• Liver enzyme inducers (e.g., phenytoin, rifampin) These interactions may require dose adjustments or avoidance.

7. Is Ondansetron included in the WHO essential medicines list?

Yes. Ondansetron is recognized by the World Health Organization as an essential medicine for its effectiveness in managing nausea and vomiting.

8. Can Ondansetron be combined with other antiemetics?

Absolutely. Ondansetron