Palonosetron: A second generation 5-hydroxytryptamine 3 receptor antagonist Palonosetron Navari

Indiana University School of Medicine South Bend, Walther Cancer Research Center, University Notre Dame, South Bend, IN 46617, USA.
Expert Opinion on Drug Metabolism &amp Toxicology (Impact Factor: 2.83). 12/2009; 5(12):1577-86. DOI: 10.1517/17425250903407289
Source: PubMed


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 characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV.
This review provides a detailed description of palonosetron, a second generation 5-HT3 receptor antagonist.
The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials.
Palonosetron has a longer half-life and a higher binding affinity than the first generation 5-HT3 receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials that were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation.

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    • "The observed differences in efficacy in the delayed phase for palonosetron versus other 5-HT3 RAs may be partly explained by the drug’s pharmacology.57 Palonosetron has a longer half-life and greater 5-HT3 receptor binding affinity compared with other 5-HT3 RAs.58 Palonosetron has a unique binding profile (allosteric binding and positive cooperativity) that differs from that of other 5-HT3 RAs59 and triggers receptor internalization, inducing prolonged inhibition of receptor functioning.60 Finally, palonosetron inhibits cross-talk between 5-HT3 and NK1 signaling pathways.61 "
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    ABSTRACT: Prevention of chemotherapy-induced nausea and vomiting (CINV) is a key component of treatment for patients with cancer. Guidelines are available to assist prescribers in the management of CINV associated with single-day chemotherapy regimens. However, currently there are no clear guidelines for management of CINV in patients receiving multiple-day chemotherapy regimens. Serotonin (5-HT3) receptor antagonists are a mainstay in preventing CINV, and palonosetron, given its longer half-life and duration of action relative to other 5-HT3 receptor antagonists, may be a useful option for managing CINV in multiple-day chemotherapy. Here we provide an overview of CINV and CINV treatment options, with a focus on palonosetron. We describe existing challenges in managing CINV, and discuss two patients receiving multiple-day chemotherapy, in whom CINV was managed successfully with palonosetron.
    Cancer Management and Research 09/2014; 6:329-37. DOI:10.2147/CMAR.S68102
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    • "Adverse effects of 5-HT3 receptor antagonists are not clinically serious; headache and dizziness are most commonly reported [8,17]. No difference was found in the incidence of adverse effects between ramosetron and palonosetron groups in the present study and most side-effects were mild and transient. "
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    ABSTRACT: Postoperative nausea and vomiting (PONV) is a common complication after anesthesia and surgery; 5-hydroxytryptamine type 3 (5-HT) receptor antagonists have been considered as a first-line therapy. Ramosetron and palonosetron are more recently developed drugs and have greater receptor affinity and a longer elimination half-life compared with older 5-HT receptor antagonists. The purpose of this study was to determine which drug is more effective for preventing PONV between ramosetron and palonosetron. We enrolled 100 patients undergoing gynecological laparoscopic surgery into this study. The subjects were divided into ramosetron group and palonosetron group. The medications were provided immediately before the induction of anesthesia. The occurrence of nausea and vomiting, severity of nausea according to a visual analogue scale, and rescue anti-emetic drug use were monitored immediately after the end of surgery and at 0-6 h, 6-24 h, and 24-48 h post-surgery. The incidence of vomiting was significantly lower in the palonosetron group than in the ramosetron group during 0-6 h (6% vs 26%, P = 0.012) and 0-48 h (14% vs 34%, P = 0.034). The incidence of nausea and overall PONV, and the use of rescue antiemetic were not significantly different during all time intervals. The severity of nausea was not different between the two groups. In conclusion, the incidence of PONV between the ramosetron and the palonosetron group have not shown the difference during 0-48 h, although palonosetron results in a lower incidence of vomiting during 0-6 h post-surgery.
    Korean journal of anesthesiology 02/2013; 64(2):133-7. DOI:10.4097/kjae.2013.64.2.133
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    ABSTRACT: The present review gives an overview on the serotonin (5-hydroxytryptamine; 5-HT) system, its receptors and their relationship to central nervous system physiology and disorders. Additionally, we also introduce the recent knowledge about the 5-HT receptor ligands in preclinical research, clinical trials and as approved drugs.
    Pharmacological reports: PR 09/2009; 61(5):761-77. DOI:10.1016/S1734-1140(09)70132-X · 1.93 Impact Factor
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