Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palonosetron, a selective 5-HT3 receptor antagonist, is being developed by Helsinn for the potential treatment of chemotherapy-induced nausea and vomiting. By 1999, it was in phase III trials, and as of May 2002, an NDA filing was scheduled for the third quarter of 2002.
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PMID:Palonosetron (Helsinn). 1243 Oct 27

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 (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Although the 5-HT3 receptor antagonists, dexamethasone, and metoclopramide have been used to prevent delayed CINV, only dexamethasone appears to have much efficacy with acceptable toxicity. Recent studies have introduced two new agents, palonosetron and aprepitant, for the prevention of both acute and delayed CINV. Palonosetron is a new 5-HT3 receptor antagonist with a longer half life and a higher binding affinity than older 5-HT3 receptor antagonists. It improves the complete response rate (no emesis, no need for rescue) of acute and delayed CINV in patients receiving moderately emetogenic chemotherapy compared to the older 5-HT3 receptor antagonists. The other agent, aprepitant, is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when compared to placebo and when used in combination with dexamethasone compared to dexamethasone alone. Acute and delayed nausea may also be improved by aprepitant when used in combination with a 5-HT3 and dexamethasone prechemotherapy or with daily dosing for 3-5 days following chemotherapy. Based on these studies, new guidelines for the prevention of CINV are proposed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.
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PMID:Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--two new agents. 1535 52

Nausea and vomiting are typical side effects of cytotoxic therapy and some surgical procedures. These symptoms can represent a major therapeutic challenge and, if inadequately controlled by antiemetic treatment, will result in increased mortality, morbidity, and health care costs. However, the management of nausea and vomiting has improved greatly in recent years following the introduction of the 5-HT3-receptor antagonists, known as 'setrons.' In light of recent developments in antiemetic care, including the approval of the first neurokinin-1-receptor antagonist aprepitant (Emend; Merck and Company, Inc.; West Point, PA) and a new 5-HT3 receptor antagonist palonosetron (Aloxi; MGI Pharma; Minneapolis, MN), this article provides an update on the clinical experience gained with the 5-HT3-receptor antagonist granisetron (Kytril; Roche Laboratories, Inc.; Nutley, NJ) for the management of chemotherapy-induced, radiation-induced, and postoperative nausea and vomiting, and also reviews its use in special patient populations. Granisetron is a potent and highly selective 5-HT3-receptor antagonist that has little or no affinity for other receptors, a characteristic that is thought to underlie the favorable side-effect and safety profiles of this agent. Extensive clinical trial data have shown granisetron to be an effective and well-tolerated agent for the treatment of nausea and vomiting in the oncology and surgical settings. Granisetron has also been shown to be effective and well tolerated in special populations, such as patients refractory to antiemetic treatment, patients with hepatic or renal impairment, and children. Data also suggest that its safety profile and minimal potential for drug-drug interactions would make it an antiemetic agent of choice for elderly cancer patients.
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PMID:Granisetron: an update on its clinical use in the management of nausea and vomiting. 1556 11

Despite the advance in supportive care that occurred with the introduction of selective serotonin subtype 3 (5-HT3) receptor antagonists, control of chemotherapy-induced nausea and vomiting (CINV) with first-generation agents (ondansetron, dolasetron, and granisetron) is less than ideal. Palonosetron is a unique 5-HT3 receptor antagonist whose distinctive pharmacologic characteristics (ie, high 5-HT3 receptor binding affinity, prolonged half-life) result in superior clinical benefit. Superiority of palonosetron over ondansetron and dolasetron in the prevention of both acute and delayed CINV has been observed in each phase III trial conducted. Of note, such evidence of superiority has never been seen in US Food and Drug Administration (FDA) registration trials of other approved agents in this class. Recently approved by the FDA, palonosetron 0.25 mg intravenously is indicated for the prevention of acute nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy. Unlike other 5-HT3 receptor antagonists, palonosetron is also indicated for prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Palonosetron exhibits an excellent tolerability profile, with frequency, severity, and duration of adverse reactions similar to that of comparator agents. Unlike older agents that are considered therapeutically interchangeable at equipotent doses, palonosetron should be considered a clinically distinct and superior treatment for the prevention of CINV.
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PMID:Palonosetron: a unique 5-HT3 receptor antagonist indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. 1616 94

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 (female gender, younger age, no alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have recently been approved for the prevention of both acute and delayed CINV. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 receptor (NK-1) antagonists. There are a number of 5-HT3 receptor antagonists and NK-1 receptor antagonists currently in Phase II and III clinical trials. Revised antiemetic guidelines for the prevention of CINV are reviewed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.
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PMID:Emerging drugs for chemotherapy-induced emesis. 1650 32

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 (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine (5-HT)3 receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a clinical problem. A new agent, palonosetron, has recently 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. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. In a single dosing study, palonosetron was highly effective in controlling CINV compared with a single dose of dolasetron or ondansetron in patients receiving moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone demonstrated control of CINV in patients receiving highly emetogenic chemotherapy. Palonosetron appeared to be as effective in subsequent courses of chemotherapy compared with the initial course of chemotherapy. There were no clinically relevant differences seen among palonosetron, ondansetron or dolasetron in laboratory, electrocardiographic or vital-sign changes, and adverse reactions reported in the clinical trials were the most common reactions reported for the 5-HT3 receptor antagonist class. Recent studies using palonosetron-based anti-emetic combinations in moderately and highly emetogenic chemotherapy, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Future studies may consider the use of palonosetron with current and other new agents and in other clinical settings, such as bone marrow transplantation and radiation therapy.
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PMID:Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. 1702 51

Serotonin (5-HT3) receptor antagonists are the foundation of standard antiemetic care for cancer patients receiving emetogenic chemotherapy. To enhance the efficacy of these supportive care agents, dexamethasone is routinely admixed with the 5-HT3 receptor antagonist, which is administered by intravenous infusion before chemotherapy begins. This phase II study evaluated the safety and efficacy of intravenous palonosetron admixed with dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy. Cancer patients received palonosetron 0.25 mg plus dexamethasone 8 mg admixed in 50 mL of infusion solution before receiving at least one qualifying chemotherapeutic agent (cyclophosphamide < or = 1,500 mg/m2, doxorubicin > or = 20 mg/m2, carboplatin, or oxaliplatin). Patients used diaries to record nausea and emesis experienced and rescue medications used. Of 32 participants, 27 (84%) had a complete response (no emesis and no rescue medication) during the acute (0-24 hours) interval posttherapy, 19 (59%) had a complete response during the delayed (> 24-120 hours) posttherapeutic interval, and 19 (59%) had a complete response during the overall (0-120 hours) posttreatment interval. A total of 23 patients (72%) had no emetic episodes, 16 (50%) had no nausea, and 21 (66%) used no rescue medication throughout the overall 5-day interval. The combination was well tolerated. Palonosetron plus dexamethasone given as a pretreatment infusion is effective and safe in preventing acute and delayed CINV in patients receiving moderately emetogenic chemotherapy.
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PMID:Infusion of palonosetron plus dexamethasone for the prevention of chemotherapy-induced nausea and vomiting. 1708 Jul 35

Chemotherapy-induced nausea and vomiting (CINV) remains an important and common toxicity of cancer treatment. Recent guideline revisions have classified chemotherapeutic agents into four categories of emesis risk without the use of preventive agents: high (> 90%), moderate (30%--90%), low (10%-30%), and minimal (< 10%). Currently available antiemetic agents, including corticosteroids, 5-hydroxytryptamine (HT)3 receptor antagonists, and neurokinin (NK)-1 antagonists are used alone or in combination depending on the level of emetogenic potential as prophylaxis against the development of CINVduring the acute period (up to 24 hours after chemotherapy) and the delayed period (up to 5 days after treatment). Newer agents, including the second-generation 5-HT3 receptor antagonist palonosetron (Aloxi) and the NK-1 antagonist aprepitant (Emend), offer additional clinical benefit in highly and moderately emetogenic therapy. However, delayed nausea and vomiting continue to occur frequently in many patients and have an impact on quality of life. Other classes of agents including the benzodiazepines and cannabinoids offer the potential for additional protective benefit. Continued research with new drugs and combinations is necessary to meet this significant unmet need of cancer patients.
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PMID:Chemotherapy-induced nausea and vomiting: which antiemetic for which therapy? 1771 96

Palonosetron is a second-generation serotonin 5-HT3 receptor antagonist, with a distinct pharmacological profile that differs from first-generation 5-HT3 receptor antagonists. Intravenous palonosetron is widely indicated for the prevention of chemotherapy-induced nausea and vomiting (CINV) in the acute and delayed phases following moderately emetogenic chemotherapy (MEC) and the prevention of CINV in the acute phase following highly emetogenic chemotherapy (HEC). In the US, oral palonosetron is approved for the prevention of CINV in the acute phase following MEC (although this formulation is not currently available), and intravenous palonosetron is indicated for the prevention of postoperative nausea and vomiting (PONV) in the first 24 hours following surgery. All indications are currently limited to adult patients. Intravenous palonosetron was noninferior to intravenous ondansetron (with statistically greater efficacy than ondansetron) or dolasetron in preventing CINV following MEC, or to intravenous ondansetron or granisetron in preventing CINV following HEC, in the acute phase. Statistically greater efficacy was seen with intravenous palonosetron than ondansetron or dolasetron in preventing CINV following MEC in the delayed phase. Oral palonosetron was noninferior to intravenous palonosetron in preventing CINV in the acute phase in patients receiving MEC. Intravenous palonosetron was superior to placebo in preventing PONV in the first 24 hours following surgery. Palonosetron was generally well tolerated in clinical trials. Intravenous palonosetron is a valuable option in the prevention of acute- and delayed-phase CINV in adult patients receiving MEC, and of acute-phase CINV in patients receiving HEC. Oral palonosetron is likely to be a useful addition to oral formulations of other 5-HT3 receptor antagonists in preventing CINV in patients receiving MEC. Intravenous palonosetron is a useful alternative to currently recommended agents in PONV prevention.
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PMID:Palonosetron: in the prevention of nausea and vomiting. 1985 28

Lung cancer is the leading cause of cancer-related death for both men and women worldwide, and lung cancer also has the highest morbidity and mortality rate among all cancers in China. Chemotherapy (CT) is the most effective and most widely used treatment for lung cancer. Nausea and vomiting are still among the most unpleasant side effects of chemotherapy, especially during highly emetogenic chemotherapy. The standard therapy for preventing chemotherapy-induced nausea and vomiting (CINV) is 5-hydroxytryptamine 3 (5-HT3) receptor antagonists. Palonosetron is a highly potent second-generation selective 5-HT3 receptor antagonist with stronger binding affinity for the 5-HT3 receptor. Palonosetron showed a high antiemetic activity in preclinical study and pivotal trails enrolling patients treated with moderately or high antiemetic activity drugs. Aim of the study was to verify the activity and safety of palonosetron in patients affected by non-small-cell lung carcinoma (NSCLC) and treated with chemotherapy. Patients with stage II-IV NSCLC and receiving chemotherapy entered into the trial. Informed written consent was required. Patients were randomized to received palonosetron or ondasetron. A single pretreatment dose of palonosetron 0.25 mg intravenous followed was administered. Nausea and vomiting were evaluated over 7-day period. Also the adverse effects were reported. Adverse events were evaluated according to the NCI-CTC criteria. Eighty-nine patients were enrolled into the study. The complete responses during the acute phase were 95.4 and 93.3%, respectively. The main side effects were headache 4.5%, constipation 15.7%, anxiety 2.3%. Palonosetron is a very active antiemetic drug for the prevention of nausea and vomiting in NSCLC patients received chemotherapy.
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PMID:Palonosetron for prevention of acute and delayed nausea and vomiting in non-small-cell lung carcinoma patients. 2060 63


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