Sechenov School
Home › Pharmacology › Antiemetics: Pharmacology, Mechanism of Action, and Clinical Use

Antiemetics

*Antiemetica*

For medical students2 min readUpdated 2026-10-10

Antiemetics are pharmacological agents used to suppress nausea and vomiting of various etiologies. Their mechanism of action is based on the selective blockade of specific receptors in the central nervous system (the vomiting center and the chemoreceptor trigger zone) or in the peripheral gastrointestinal tract.

Main TargetReceptors of the vomiting center and chemoreceptor trigger zone (D₂, 5-HT₃, H₁, M-cholinergic receptors).
BBB PenetrationDetermines the presence of central adverse effects (e.g., extrapyramidal symptoms).
Oncology Choice5-HT₃ receptor antagonists are the gold standard for chemotherapy- and radiation-induced nausea and vomiting.
Strict ContraindicationProkinetics are strictly contraindicated in gastrointestinal bleeding and perforations.

Classification by Receptor Type

Antiemetics are divided into several pharmacological groups based on their specific receptor targets:

Dopamine Receptor Blockers

This group is widely used clinically, though the agents differ significantly in their ability to cross the blood-brain barrier (BBB).

Metoclopramide has a mixed mechanism of action. In the CNS, it blocks D₂ and 5-HT₃ receptors in the chemoreceptor trigger zone. Peripherally, it acts as a prokinetic: stimulating gastric motility, increasing lower esophageal sphincter tone, and relaxing the pylorus. Onset of action is rapid (5–15 minutes). It relieves hiccups and is effective for emesis following anesthesia, radiation therapy, or induced by cardiac glycosides and cytostatics. Due to BBB penetration, it can cause extrapyramidal symptoms and endocrine disorders (hyperprolactinemia, amenorrhea, gynecomastia). It is contraindicated during lactation and in patients with muscle dyskinesias.

Domperidone is a selective peripheral blocker. It poorly crosses the BBB, making it virtually free of central adverse effects. This makes it the drug of choice for vomiting caused by dopaminergic drugs (e.g., in Parkinson's disease treatment). It is used for dyspepsia and delayed gastric emptying. It is contraindicated in children under 5 years of age.

Thiethylperazine is a phenothiazine derivative with potent central action. It directly depresses the vomiting center and trigger zone. It is prescribed in courses (2–4 weeks) for vestibular disorders and motion sickness. It has a wide spectrum of adverse reactions, ranging from dry mouth and tachycardia to drowsiness, speech disorders, and hypotension. It is contraindicated in children under 15, pregnant women, and patients with depression, coma, or acute glaucoma.

Serotonin Receptor Blockers

The primary representative of this group is ondansetron. The drug blocks 5-HT₃ receptors both peripherally and in the central nervous system.

Its specific clinical niche is the prevention and management of severe nausea and vomiting induced by cytotoxic chemotherapy and radiation therapy in cancer patients. It is highly effective but has strict limitations: it is contraindicated in the first trimester of pregnancy and during lactation. Common adverse effects include headache, constipation, dizziness, and arterial hypotension.

Histamine and Cholinergic Receptor Blockers

Drugs in these groups are particularly relevant for kinetoses (motion sickness) and vestibular disorders.

Meclizine provides combined blockade of central H₁-histamine and M₁-cholinergic receptors. It features a rapid onset and very long duration of action (approximately 24 hours). It is used for air and motion sickness, as well as for radiation-induced emesis.

Aeron is a combination drug consisting of camphorate salts of alkaloids (scopolamine and hyoscyamine). It exerts central and peripheral antimuscarinic effects. It is effective for preventing motion sickness and managing sudden vertigo attacks in Ménière's disease. However, it causes typical atropine-like effects (thirst, dry mouth) and is strictly contraindicated in glaucoma due to the risk of increased intraocular pressure.

Mnemonic

To remember domperidone's safety profile: "Domperidone — a DOM (home) for the PERIphery." It works predominantly in the periphery (poor BBB penetration), making it safe for Parkinson's disease patients because it does not block the central dopamine they require.

Frequently asked questions

Which antiemetic drugs are phenothiazine derivatives?

Thiethylperazine is an antiemetic drug that belongs to the phenothiazine derivatives.

  • Thiethylperazine is an effective centrally acting blocker that directly inhibits the activity of the vomiting center and the trigger zone.

Its mechanism of action is based on the blockade of central $\text{D}_2$ receptors. The drug is used for vomiting of any origin and vestibular disorders (dizziness, motion sickness).

What adverse effects are typical for ondansetron?

Ondansetron is associated with several adverse effects involving the nervous, cardiovascular, and digestive systems, including:

  • Headache (cephalalgia);
  • Dizziness;
  • Arterial hypotension;
  • Constipation — occurs due to slowed intestinal motility with repeated administration;
  • Allergies — various hypersensitivity reactions.

Notably, ondansetron does not impair motor coordination or patient performance.

What types of receptors are present in the chemoreceptor trigger zone of the vomiting center?

The chemoreceptor trigger zone of the vomiting center contains two main types of receptors:

  • Dopamine receptors ($D_2$ receptors);
  • Serotonin receptors ($5-HT_3$ receptors).

These receptors respond to chemical substances in the blood and cerebrospinal fluid, and their blockade by specific drugs (e.g., metoclopramide) provides central antiemetic effects.

Which antiemetic agents belong to the NK1 receptor blocker group?

Neurokinin-1 (NK-1) receptor antagonists (blockers) include the following antiemetic drugs:

  • Aprepitant — a selective, high-affinity, centrally acting antagonist that binds to brain receptors and is administered orally;
  • Fosaprepitant — a prodrug formulated for intravenous administration.

These agents inhibit both the acute and delayed phases of emesis and enhance the antiemetic activity of glucocorticoids and $5-HT_3$ receptor antagonists.

Why is metoclopramide contraindicated in suspected GI perforation?

Metoclopramide has strong prokinetic activity, actively stimulating propulsive gastric motility. In ulcers, bleeding, or perforations, enhanced peristalsis can lead to a drastic worsening of the patient's condition.

Which drug should be chosen to manage post-chemotherapy emesis?

The drugs of choice in oncology practice are 5-HT₃ receptor antagonists (e.g., ondansetron, tropisetron). They specifically and effectively suppress the emetic reflex triggered by cytostatics.

What is the main difference between domperidone and metoclopramide?

Domperidone practically does not cross the blood-brain barrier. Consequently, it does not cause central extrapyramidal symptoms characteristic of metoclopramide and neuroleptics.

Can *Aeron* be used in glaucoma?

No, Aeron is strictly contraindicated in glaucoma. As an antimuscarinic agent, it can elevate intraocular pressure, potentially precipitating an acute attack of the disease.

Go deeper

More topics in Pharmacology

Halogens and Halogen-Containing CompoundsTolbutamideAtropine SulfateCyanocobalaminQuinineAlpha-2 Adrenergic Agonists: Mechanism and Clinical UseCarbamazepineThiazide DiureticsErgot AlkaloidsCardiac GlycosidesNatamycin: Mechanism, Spectrum and Clinical UsesTetracaine: Pharmacology, Mechanism and Clinical UsePharmacology →