Description

Aprepitant is an antiemetic drug that belongs to a class of medications called neurokinin-1 (NK1​) receptor antagonists. It is a synthetic substance that works by blocking the action of a specific neurotransmitter in the central nervous system. It is available in oral capsules and as a prodrug for intravenous administration (fosaprepitant).

Indications

Aprepitant is used in adults and children for the prevention of nausea and vomiting, particularly those associated with highly or moderately emetogenic (vomit-inducing) therapies. It is not intended to treat existing nausea or vomiting. Its main indications include:

• Chemotherapy-induced nausea and vomiting (CINV): Aprepitant is used in combination with other antiemetic drugs, such as a serotonin 5-HT3​ receptor antagonist and a corticosteroid (e.g., dexamethasone), for the prevention of both acute (within 24 hours) and delayed (1-5 days after) nausea and vomiting associated with highly emetogenic cancer chemotherapy.

• Postoperative nausea and vomiting (PONV): It is also used for the prevention of nausea and vomiting following surgery.

Mechanism of Action

Aprepitant’s mechanism of action is based on its ability to block the effects of a specific neuropeptide called Substance P.

1. Targeting the NK1​ Receptor: Aprepitant is a selective antagonist of the neurokinin-1 (NK1​) receptor. These receptors are found in various parts of the body, including the central nervous system, where they play a key role in the emetic reflex.
2. Blocking Substance P: The natural ligand (the substance that binds to and activates) for theNK1​ receptor is Substance P. Substance P is a neuropeptide that transmits signals of nausea and vomiting to the brain, particularly in the brainstem’s “vomiting center” and chemoreceptor trigger zone.

3. Inhibition of the Emetic Reflex: By blocking the NK1​ receptors, aprepitant prevents Substance P from binding and activating them. This action effectively inhibits the nausea and vomiting signal transmission from the gut and brain to the vomiting center.
4. Synergistic Effect: Aprepitant is particularly effective because it works on a different pathway from other common antiemetics like serotonin 5-HT3​ receptor antagonists (e.g., ondansetron) and corticosteroids. By combining these different mechanisms, the overall antiemetic effect is enhanced, providing more comprehensive control over both acute and delayed nausea and vomiting.

In summary, aprepitant’s action is to block the Substance P/NK1​ pathway, thereby interrupting a key signaling route for the emetic reflex, making it a powerful tool for preventing chemotherapy- and surgery-induced nausea and vomiting.