Serotonin Antagonists (Setrone)

Products

Serotonin receptor antagonists are commercially available in the form of film-coated tablets, melting tablets, soft capsules, as syrups, and as infusion/injection preparations. This article refers to the setrone (5-HT₃ receptor antagonists), which are used as antiemetics. The first agent from this group to be approved in the United States was ondansetron (Zofran) in 1991, which was developed in the 1980s.

Structure and properties

Serotonin antagonists have some structural similarity to the natural ligand serotonin. They are characterized by various nitrogen heterocycles, for example, carbazole, indazole, and indole. The nonselective precursors of the drug group are metoclopramide and cocaine, also antagonists at this receptor subtype.

Effects

The setrons (ATC A04AA) have antiemetic properties, meaning they are effective against nausea and vomiting. They are selective and competitive antagonists at serotonin-5-HT₃ receptors, acting both centrally and peripherally in the digestive tract. Chemotherapy leads to release of serotonin from enterochromaffin cells in the intestine. The setrons inhibit peripheral transmission of the signal from the gut to the brain via afferent nerves of the vagus nerve.

Indications

• Nausea and vomiting induced by cytotoxic chemotherapeutic agents or radiotherapy.
• Postoperative nausea and vomiting.

Dosage

According to the SmPC. Serotonin antagonists are administered perorally and parenterally, as intravenous injection or infusion.

Active Ingredients

Antiemetics:

• Granisetron (Kytril, generic).
• Ondansetron (Zofran, generic).
• Palonosetron (Aloxi, Akynzeo, generic).

Out of commerce or not on sale in many countries:

• Dolasetron (Anzemet, out of commerce).
• Ramosetron
• Tropisetron (Navoban, out of commerce).

Contraindications

Contraindications include:

• Hypersensitivity
• Combination with apomorphine (ondansetron).
• Use during pregnancy is not recommended. Studies with ondansetron have shown a higher risk of birth defects.

For complete precautions, see the drug label.

Interactions

Setrons are substrates of CYP450 isoenzymes. Other interactions have been described with apomorphine (contraindicated with ondansetron) and with serotonergic drugs. Setrons should be combined only with caution with drugs that prolong the QT interval.

Adverse Effects

Common possible adverse effects of setrone include:

• Feeling of warmth
• Headache, dizziness
• Constipation, diarrhea

The drugs may prolong the QT interval and rarely cause cardiac arrhythmias. Appropriate precautions must be observed.