5-HT3 receptors as important mediators of nausea and vomiting due to chemotherapy.

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24 h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24-120 h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy-induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

• Authors: Rudolph M Navari
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1848 Issue 10 Pt B Pg. 2738-46 (Oct 2015) ISSN: 0006-3002 [Print] Netherlands
• PMID: 25838122 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antiemetics
• Antineoplastic Agents
• Isoquinolines
• Neurokinin-1 Receptor Antagonists
• Quinuclidines
• Receptors, Neurokinin-1
• Receptors, Serotonin, 5-HT3
• Serotonin 5-HT3 Receptor Antagonists
• Benzodiazepines
• Palonosetron
• Dexamethasone
• Olanzapine

Topics

• Antiemetics (pharmacokinetics, therapeutic use)
• Antineoplastic Agents (administration & dosage, adverse effects)
• Benzodiazepines (pharmacokinetics, therapeutic use)
• Dexamethasone (pharmacokinetics, therapeutic use)
• Half-Life
• Humans
• Isoquinolines (pharmacokinetics, therapeutic use)
• Nausea (chemically induced, metabolism, physiopathology, prevention & control)
• Neoplasms (drug therapy, pathology)
• Neurokinin-1 Receptor Antagonists (pharmacokinetics, therapeutic use)
• Olanzapine
• Palonosetron
• Quality of Life
• Quinuclidines (pharmacokinetics, therapeutic use)
• Receptors, Neurokinin-1 (metabolism)
• Receptors, Serotonin, 5-HT3 (metabolism)
• Serotonin 5-HT3 Receptor Antagonists (pharmacokinetics, therapeutic use)
• Vomiting (chemically induced, metabolism, physiopathology, prevention & control)