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)

To address the economic issues posed by the introduction of 5-hydroxytryptamine3 receptor antagonist (5-HT3 RA), we performed a cost-effectiveness analysis based on clinical trial data published in the recent literature. Cost calculations include initial treatment and a second-line salvage treatment. The average cost and incremental cost were established. Incremental cost corresponds to the extra cost involved in achieving total control of emesis in 1% extra patients. If 5-HT3 RA is not part of the initial treatment, salvage treatment with ondansetron is not cost-effective. Moreover, starting with the combination of ondansetron plus dexamethasone saves more money than starting with ondansetron alone. However, if the difference in emesis control is only minimal, treatment with the 5-HT3 RA remains more expensive.
Support Care Cancer 1994 May
PMID:Cost-effectiveness analysis of antiemetic treatment. 803 96

Chemotherapy-related nausea and vomiting can today be controlled with available antiemetics in a high percentage of patients but emesis remains a problem for some patients, with certain drugs and with repeated cycles of chemotherapy. The fundamental steps of clinical research in antiemetics towards the improvement of the control of nausea and vomiting with new drugs or combinations are presented. Special emphasis is given to cisplatin-induced nausea and vomiting because of the frequency and relevance of this phenomenon. The use of high-dose metoclopramide, its combination with steroids, and later the addition of lorazepam or diphenhydramine represented the evolving standard of the 1980s, with the level of complete protection from vomiting improving from 30%-40% to 60%-70% with the three-drug combination. The introduction of new agents such as the 5-hydroxytryptamine 3 (5-HT3) receptor antagonists has recently offered new possibilities because of their activity and lack of toxicity. In particular, the combination of ondansetron plus dexamethasone is today the most efficacious and least toxic antiemetic treatment for prevention of emesis in patients treated with a single high dose or low repeated doses of cisplatin. A comparison of different 5-HT3 antagonists, always in combination with steroids, is now considered necessary. For patients treated with moderately emetogenic chemotherapy the use of steroids can still be considered the standard treatment. In this setting, the role of 5-HT3 receptor antagonists, alone or in combination with steroids, has to be better defined through large, well-planned clinical trials, which should have a cost-effectiveness analysis as one of their goals.
Support Care Cancer 1994 May
PMID:Antiemetics in cancer chemotherapy: historical perspective and current state of the art. 803 96

Granisetron is the second agent in the 5-HT3 receptor antagonist class to be approved for the prophylaxis of acute emesis caused by cancer chemotherapy. It is equally effective to ondansetron as a first-line agent in the prevention of acute chemotherapy-induced emesis and has a similar low toxicity profile. Granisetron will be marketed in early 1994, according to SmithKline Beecham. Additional studies will be needed to determine the role of granisetron in the current management of chemotherapy-induced emesis.
Cancer Pract
PMID:Granisetron. 805 27

Emesis and nausea are common toxicities seen during high-dose interleukin-2 (IL-2) therapy (720,000 IU/kg i.v. every 8 h). A growing list of randomized studies have documented the efficacy of ondansetron, a potent antagonist of the 5-hydroxytryptamine3 receptor, in preventing acute chemotherapy-induced emesis and nausea. However, no study has evaluated the efficacy of ondansetron in preventing IL-2-induced emesis and nausea. This double-blinded, randomized trial was performed to compare the antiemetic and antinausea efficacy of ondansetron with that of droperidol, a butyrophenone, in patients receiving high-dose IL-2 on protocols at the National Cancer Institute. Ondansetron or droperidol was given intravenously, 30 min prior to the first dose of IL-2 and then every 8 h for the duration of IL-2 treatment. No significant differences were seen between the two agents in complete freedom from emesis (p2 = 0.51), level of nausea (p2 = 0.17), antiemetic treatment failure (p2 = 0.89), and time to first emetic episode (p2 = 0.44). Equivalent doses of IL-2 were administered on each arm of the study, with a similar incidence of liver dysfunction (p2 = 0.15) and diarrhea (p2 = 0.64). Finally, there was no significant difference in the response rates to metastatic disease in either arm of the antiemetic study (p2 = 0.67), and these response rates were similar to those in other patients treated under immunotherapy protocols in the Surgery Branch of the National Cancer Institute with high-dose IL-2. We conclude that droperidol is equally effective in preventing emesis and controlling nausea when compared with ondansetron for patients receiving high-dose IL-2.
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PMID:A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2. 808 60

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.
Support Care Cancer 1994 Jul
PMID:The anti-emetic efficacy and tolerability of tropisetron in patients conditioned with high-dose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation. 808 43

The management of chemotherapy-induced nausea and emesis presents a major problem in children with cancer. The anti-emetic properties of the 5-HT3 receptor antagonist ondansetron are well documented in adults receiving cytotoxic chemotherapy. Experience in the treatment of children is still limited. Here we present a review of the literature on the anti-emetic treatment with ondansetron in children. Moreover, we provide recommendations on the use of ondansetron during anti-neoplastic chemotherapy and radiotherapy in pediatric oncology.
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PMID:Ondansetron in the control of chemotherapy-induced and radiotherapy-induced emesis in children with malignancies. 813 11

This paper described an outline of pharmacological studies of 5-HT3 receptor antagonists, mainly on ondansetron, which control nausea and vomiting associated with cancer chemotherapy. Administration of cytotoxic drugs is known to increase serotonin (5-HT) concentrations, and when released, 5-HT provokes the emetic responses via two routes; 1) 5-HT acts as an intrinsic transmitter substance and stimulates the emetic response via 5-HT3 receptors on vagal afferent terminals; 2) 5-HT transmits impulses to the vomiting center via 5-HT3 receptors on the chemoreceptor trigger zone in the area postrema of the central nervous system. 5-HT3 receptor antagonists are thought to exert an antiemetic action by specifically and competitively blocking 5-HT3 receptors.
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PMID:[An outline of 5-HT3 receptor antagonists (1)--In pharmacological actions]. 823 73

Combinations of drugs have become standard therapy for the prevention of vomiting caused by anticancer drugs like cisplatin. Recently, a new class of antiemetic agents, the potent and specific 5-HT3 receptor antagonists such as ondansetron, granisetron, and tropisetron, have been shown to be more effective and better tolerated than metoclopramide. This report describes the rationale for combination antiemetic therapy, details the testing of metoclopramide-based regimens as a model for combination therapy development, reviews completed trials of ondansetron plus dexamethasone, and offers strategies to further alleviate vomiting during anticancer chemotherapy. The reported trials testing metoclopramide-based combinations were reviewed and that experience was applied to the ongoing studies of ondansetron when used with dexamethasone and other agents. Combinations of metoclopramide, dexamethasone, and lorazepam prevented acute emesis caused by high-dose cisplatin in 63% of patients, lessened side effects, and were convenient enough to administer to outpatients. Completed trials of ondansetron and dexamethasone demonstrated improved vomiting control over ondansetron alone while using less cumbersome schedules. Attempts to improve ondansetron-based antiemetic regimens by developing optimal drug doses and schedules and adding adjuvant and different classes of antiemetic agents are now in clinical testing. Based on previous experience and current results, combinations of a specific serotonin agonist and dexamethasone are the best treatment for prevention of vomiting induced by chemotherapy. Future clinical research should aim to refine antiemetic regimens and improve emetic control through the use of new antiemetic and adjuvant agents.
Cancer 1993 Dec 01
PMID:Enhancing the effectiveness of the specific serotonin antagonists. Combination antiemetic therapy with dexamethasone. 824 76

This paper described an outline of clinically applications of 5-HT3 receptor antagonists, mainly on ondansetron, which control nausea and vomiting associated with cancer chemotherapy. Clinically, 5-HT3 receptor antagonists demonstrated significantly superior antiemetic effects to metoclopramide which has been prescribed for relatively long time. The response rates for granisetron and those for ondansetron were different due to the different categorical scales. However, when the same scale was applied, similar efficacies have been observed. Introduction of the tablet form may well broaden the clinical applications. Considering the highly evaluated safety, 5-HT3 receptor antagonists, from the viewpoints of clinical usefulness and safety, seems to be useful drugs for controlling nausea and vomiting associated with cancer chemotherapy.
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PMID:[An outline of 5-HT3 receptor antagonists (2)--In clinical applications]. 825 39

The interactions of the antiemetic metopimazine (MPZ) and of the chemotherapeutic agents, cisplatin, carboplatin, doxorubicin, etoposide and vincristine were investigated at five neurotransmitter receptor binding sites. MPZ had nanomolar affinity for alpha 1, dopamine D2 and histamine H1 receptors, weak affinity for muscarinic cholinergic receptors, but no affinity for 5-hydroxytryptamine3 (5-HT3) receptors. Except for vincristine, which showed nanomolar affinity of muscarinic cholinergic receptors, none of the chemotherapeutic agents showed affinity for any of the receptors investigated at concentrations ranging between 10(-5) and 10(-7) M. Accordingly, chemotherapy-induced nausea and vomiting seems to be mediated by mechanisms other than the direct interaction of cytostatics with the neurotransmitter receptors investigated. Our finding that MPZ is without affinity for 5-HT3 receptors and therefore seems to mediate its antiemetic effect predominantly by dopamine D2 receptor blockade makes it an interesting drug for use in combinations with the new class of antiemetics, the 5-HT3 receptor antagonists. Data obtained in a recent clinical trial support this observation.
Cancer Chemother Pharmacol 1993
PMID:Interaction of the antiemetic metopimazine and anticancer agents with brain dopamine D2, 5-hydroxytryptamine3, histamine H1, muscarine cholinergic and alpha 1-adrenergic receptors. 826 89


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