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01-09-2000 | Leading Article

Potential of Substance P Antagonists as Antiemetics

Authors: Dr Pierre Diemunsch, Laurent Grélot

Published in: Drugs | Issue 3/2000

Abstract

The introduction of serotonin 5-HT3 receptor antagonists into clinical practice allowed for a dramatic improvement in the management of nausea and vomiting. Despite this, postoperative and chemotherapy-induced emesis remains a significant, unresolved issue in many patients even when a combination of antiemetic drugs is used. Numerous neurotransmitters have been implicated in triggering emesis; however, the tachykinin substance P, by virtue of its localisation within both the gastrointestinal vagal afferent nerve fibres and brainstem emetic circuitry, and its ability to induce vomiting when administered intravenously, is thought to play a key role in emetic responses. Because substance P is the most likely endogenous ligand for the neurokinin-1 (NK₁) receptor, the development of nonpeptide NK₁ receptor antagonists led scientists to evaluate these compounds as antiemetics. The five NK₁ receptor inhibitors that have been studied initially in humans are: vofopitant (GR-205171), CP-122721, ezlopitant (CJ-11974), MK-869 (L-754030) and its prodrug L-758298. Except for monotherapy in acute cisplatin-induced emesis, this new class of drugs has proven to be highly effective in the control of both chemotherapy-induced nausea and vomiting, and postoperative nausea and vomiting. No major adverse event was reported in the preliminary trials. Further investigation is mandatory in order to assess the optimal treatment regimen and to make sure the wide spectrum activity of the NK₁ receptor inhibitors does not cause significant adverse effects in the context of the treatment of nausea and vomiting.

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Title: Potential of Substance P Antagonists as Antiemetics
Authors: Dr Pierre Diemunsch
Laurent Grélot
Publication date: 01-09-2000
Publisher: Springer International Publishing
Published in: Drugs / Issue 3/2000
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200060030-00002

ACC 2024 Congress

Springer Medicine

Potential of Substance P Antagonists as Antiemetics

Abstract

ACC 2024 Congress

Springer Medicine

Abstract

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