title: 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.affiliation: Cancer Care Program, Eastern Europe, World Health Organization; Indiana University School of Medicine South Bend, USA; South Bend Medical Services Corporation, USA. Electronic address: rmnavari@gmail.com.
authors.forename: Rudolph M
authors.initials: RM
authors.lastname: Navari
mesh_terms: D000932:Antiemetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000627:therapeutic use; D003907:Dexamethasone / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D064729:Neurokinin-1 Receptor Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077152:Olanzapine; D000077924:Palonosetron; D011788:Quality of Life; D011812:Quinuclidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D064729:Neurokinin-1 Receptor Antagonists; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D001569:Benzodiazepines; D000077924:Palonosetron; D003907:Dexamethasone; D000077152:Olanzapine
keywords: 5-HT(3) receptor antagonists; Antiemetics; Chemotherapy-induced nausea and vomiting; Serotonin