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Anesthesiology NewsDopamine-antagonist Antiemetics in PONV Management: Entering a New Era?

The treatment of post-operative nausea and vomiting might undergo a revolution thanks to the resurgence of interest in D2-antagonists, particularly amisulpride.

Unraveling the history and evolution of dopamine D2-receptor antagonists, this article offers a comprehensive review of their use in managing post-operative nausea and vomiting (PONV), highlighting a renewed interest in this class of medications due to the advent of a safer agent, amisulpride.

Key Points:

  • In the late 20th century, dopamine D2-receptor antagonists, specifically droperidol, were a key tool for managing post-operative nausea and vomiting (PONV). Their use declined due to growing safety concerns, leading to an FDA black box warning.
  • A new D2-antagonist, amisulpride, approved by the FDA for PONV prevention and rescue treatment, has triggered renewed interest in this class of drugs.
  • The different structural subclasses of D2-antagonists – substituted benzamides, butyrophenones, and phenothiazines – have distinct pharmacologic properties and side effect profiles.
  • D2-antagonists can have severe side effects including neuropsychiatric effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and hyperprolactinemia. These effects can still be highly impactful even with a reduction in frequency.
  • Amisulpride, a substituted benzamide D2-antagonist, has lower side effects due to its preferential binding in the limbic system and lesser brain penetration.
  • The fourth consensus guidelines for PONV management published in 2020 emphasized multimodal PONV prophylaxis even for patients with only one or two risk factors, and the use of an antiemetic from a different pharmacologic class for PONV treatment.

Additional Points:

  • Benzamides, butyrophenones, and phenothiazines all have unique impacts and side effects. Amisulpride and metoclopramide are benzamides, droperidol and haloperidol are butyrophenones, and prochlorperazine and promethazine are phenothiazines.
  • Some D2-antagonists can interact with other drugs, creating additional risks such as QT prolongation, tardive dyskinesia, and neuroleptic malignant syndrome.
  • D2-antagonists should be used cautiously in certain populations, such as those over 65 and pediatric patients, due to potential side effects.


  • Despite their side effects, D2-antagonists can effectively manage PONV, especially with the introduction of amisulpride. Further studies comparing amisulpride to other single agent antiemetics and cost-benefit analyses are warranted.

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Did You Know?
It is estimated that about 30% of all surgical patients experience post-operative nausea and vomiting (PONV), with some high-risk populations seeing incidences as high as 80%.

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