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)

Control of chemotherapy-induced nausea and vomiting is a major concern for patients receiving cancer therapy and a major quality of life issue. However, the fact that antiemetic control improves quality (but not duration) of survival and the significant cost of newer antiemetic agents have led to discussions about the relative priority of supportive care interventions and the appropriate use of newer and more expensive medications. Various decision trees can be constructed to estimate appropriate use and pricing of the 5-HT3 receptor antagonists. Additional costs of ineffective antiemetic therapy can be taken into account when calculating the advantages of effective antiemesis. Use of appropriate doses for appropriate indications will also have an impact. Since supportive care leads to qualitative rather than quantitative improvement in survival, the appropriate form of analysis is not cost-effectiveness (which considers only increase in years of survival) but rather cost-utility (which considers quality-adjusted life years).
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PMID:Economic impact of antiemesis. 860 47

Chemotherapy-induced emesis is dependent not only on individual parameters but also on treatment parameters (type and dose of the cytotoxic drug, combination with other cytotoxic drugs). Cyclophosphamide-based chemotherapy is potentially emetogenic and the emtogenicity is proportionally dependent on the dose. Therefore, the preventive antiemetic treatment must be adapted to this emetogenic risk. A number of studies have assessed the efficacy of ondansetron, a highly selective 5-HT3 receptor antagonist, for the control of 'non cisplatin' chemotherapy. In mild emetogenic regimens, oral ondansetron is more effective than placebo and its efficacy is similar to the classic antiemetic regimen metoclopramide-dexamethasone. Concerning moderately emetogenic chemotherapies, iv ondansetron is highly effective and its effecicay is superior to that of metoclopramide and alizapride. Delayed nausea and vomiting can be controlled by an oral ondansetron treatment. This allows to maintain the good response obtained by the initial antiemetic regimen. With very high doses of cyclophosphamide, as in conditioning chemotherapy and total body irradiation prior to bone marrow transplantation, no optimal antiemetic treatment has still been defined; but the combination of ondansetron with dexamethasone should be used according to the poor control obtained with ondansetron alone. However, studies combining 5-HT3 receptor antagonists with dexamethasone are warranted in order to define the optimal treatment in this particularly emetogenic treatment setting.
Bull Cancer 1996 Jan
PMID:[Optimal control by ondansetron of acute and prolonged emesis induced by chemotherapy without cisplatin]. 867 59

In the latter part of the 20th century, significant advances have been made in the understanding of the emetic reflex. As a result, there have been major improvements in the treatment of vomiting, particularly that associated with chemo- and radiotherapeutic treatments for neoplastic disease. The 5-HT3 receptor antagonists (ondansetron and granisetron) have been demonstrated to be of benefit in treating the profound emesis observed during cancer treatment. This observation, together with results from pharmacologic and physiologic investigations in both animals and humans, have identified 5-hydroxy-tryptamine (5-HT or serotonin) to be of fundamental importance in the pathogenesis of emesis. 5-HT appears to be released by radiation and chemotherapeutic agents from enterochromaffin cells within the wall of the intestine, and possibly from neurons within the brainstem. Stimulation of 5-HT3 receptors, located centrally in the dorsal medulla of the brainstem and peripherally on vagal afferent terminals in the gastrointestinal tract, appears to play a pivotal role in eliciting emesis. The interaction of 5-HT with non-5-HT3 receptors, particularly 5-HT1A and 5-HT4 receptors, may be important in the emetic reflex. The development of agents that interact with these receptors may offer alternative approaches to the treatment of nausea and vomiting.
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PMID:Serotonergic mediation of vomiting. 870 63

The treatment of cancer patients has improved over the few past years. The improvement includes new chemotherapy modalities and the new treatments for side effects. The introduction over the last 5 years of 5-HT3 receptor antagonists, a recent class of antiemetic agents, and hematopoietic growth factors, has allowed oncologists to improve success rates and survival of cancer patients, by developing new cytotoxic agents and increasing drug doses and/or modifying the design and administration of conventional chemotherapy treatment schedules. At present, dose-intensifications of several cytotoxic agents are available. Pharmacomodulation with 5 FU and folinic acid is more emetogenic than 5 FU alone. In contrast, chronomodulation seems to be less emetogenic. For new cytotoxic agents and oral chemotherapy, the emetogenic potential differs according to the drug and the antiemetic treatment must be therefore adapted to each situation.
Bull Cancer 1995 Dec
PMID:[Future trends in chemotherapy and impact on the management of emesis]. 874 75

Most anticancer drugs are cytotoxic and produce various side-effects, among which nausea and vomiting are almost ubiquitous and usually extremely distressing to the patient. Cancer chemotherapy elicits two main phases of vomiting: an intense, acute phase of vomiting that occurs almost immediately following anti-cancer therapy and a milder, delayed phase of nausea and vomiting of longer duration. The mechanisms underlying the induction of nausea and vomiting after cancer chemotherapy are poorly understood but may be mediated by serotonin (5-hydroxytryptamine or 5-HT), particularly in the acute phase. Serotonin activates 5-HT3 receptors, which function as ligand-gated ion channels located either in the periphery and/or in the central nervous system to produce emesis, among other effects. The peripheral 5-HT3 receptors may be pharmacologically distinct from the central 5-HT3 receptors and may exhibit some association with GTP-binding proteins. In addition, different populations may exist as distinct subtypes of the same receptor. The 5-HT3 receptor antagonist ondansetron (GR 38032F) is effective in preventing the emesis induced by cytotoxic agents currently used in the treatment of many forms of cancer. Ondansetron has, comparatively, a much higher efficacy in the treatment of acute emesis following cancer chemotherapy than it does in the delayed phase, suggesting that the late phase of emesis may be mediated by other distinct mechanisms.
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PMID:Role of 5-hydroxytryptamine3 (5-HT3) antagonists in the prevention of emesis caused by anticancer therapy. 876 66

The serotonin 5-HT3 receptor is unique among the seven serotonin receptor "families" that have been recognized so far. It functions not as a G-protein coupled but as a direct ion channel gated receptor. Because of the varied neural functions linked to this receptor, intensive research interest has developed in recent years about its basic and clinical pharmacology, which are summarized in this review. Some new agonists and many new antagonists have been developed. These agents have a useful role as selective pharmacologic research probes, and some of them can be used therapeutically as potent and selective anti-nausea and antiemetic drugs, particularly in patients undergoing cancer chemotherapy treatment or general anesthesia procedures. Potential applications of these agents include the treatment of some behavioral disorders in mental disease, drug addiction, and certain types of pain syndromes.
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PMID:5-HT3 receptors: pharmacologic and therapeutic aspects. 878 44

In Suncus murinus, various emetic responses and the anti-emetic activity of a new 5-hydroxytryptamine3 (5-HT3) receptor antagonist, GK-128 (2-[(2-methylimidazol-1-yl) methyl benzo[f]thiochromen-1-one monohydrochloride hemihydrate), were investigated. Cancer chemotherapeutic agents, cisplatin and cyclophosphamide, dose-dependently induced emesis of long-lasting duration. The 5-HT3 receptor agonist, 2-methyl-5-HT, and copper sulfate also induced emesis of short duration. However, another 5-HT3 receptor agonist, m-chlorophenylbiguanide, was not consistently emetic. GK-128 inhibited the emetic responses induced by chemotherapeutic agents and 2-methyl-5-HT with similar potency. The anti-emetic action of GK-128 was more potent than that of ondansetron, Y-25130, granisetron and metoclopramide. The order of potency of these drugs, except granisetron, was consistent with that of their 5-HT3 receptor binding affinity in rat cortex. GK-128 failed to inhibit copper sulfate-induced emesis. These data suggest that GK-128 has a potent inhibitory effect on emesis via the 5-HT3 receptor, and that the 5-HT3 receptor involved in emesis in Suncus murinus may be different from the classically defined 5-HT3 receptor in other animals such as rats, dogs and ferrets.
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PMID:The anti-emetic activity of GK-128 in Suncus murinus. 884 9

Nausea and vomiting are the most frequently reported adverse effects of cancer chemotherapy and have a significant impact on patients' daily functioning, quality of life and compliance with chemotherapy. Summarized in this article are the recommendations for the optimal management of nausea and vomiting developed by a multidisciplinary group of health care professionals. Issues relating to chemotherapy-induced nausea and vomiting are discussed; general principles of treatment are reviewed; treatment algorithms based on emetogenicity and types of chemotherapy are presented; and the importance of issues including non-pharmacological approaches, patient education and pharmacoeconomic perspectives are considered. The goal of antiemetic therapy should be no episodes of vomiting or retching and minimal or no nausea. Data from clinical trials support the clear superiority of 5-HT3 receptor antagonists in a variety of clinical situations. Their cost must be considered not only as an isolated item from the institutional perspective, but also from the perspective of the impact of successful therapy on the patient.
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PMID:Guidelines for the optimal management of chemotherapy-induced nausea and vomiting: a consensus. 885 13

The aim of the work was to evaluate the impact of cyclophosphamide and ondansetron on serotonin metabolism measured by urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion. The pattern of urinary 5-HIAA excretion was analysed within 24 h following cyclophosphamide, epirubicin and 5-fluorouracil (FEC) chemotherapy (n = 14), ondansetron as single agent (n = 31), and in a control group (n = 62). 5-HIAA was measured by a fluorescence/polarisation immunoassay. Both FEC and ondansetron alone induced a significantly higher 5-HIAA increase following the first 12 h after drug administration when compared to the control group. The comparison of quantitative variables of 5-HIAA excretion between FEC and ondansetron failed to reveal any statistical differences. Cyclophosphamide-based chemotherapy is associated with only minor increases of 5-HIAA excretion. Analysis of 5-HIAA excretion does not help in the description of the pathophysiology of cyclophosphamide-induced emesis. In contrast to experimental data, serotonin 3 receptor antagonism with ondansetron induces an increase of 5-HIAA excretion in humans.
Support Care Cancer 1996 Sep
PMID:5-Hydroxyindoleacetic acid excretion following combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil plus ondansetron compared to ondansetron alone. 888 33

Dolasetron mesylate (MDL 73,147EF, Anzemet; Hoechst Marion Roussel, Laval, Canada) is a 5-HT3 receptor antagonist undergoing clinical evaluation for use as an antiemetic agent. The pharmacokinetics of dolasetron and its reduced metabolite (MDL 74,156) were studied after administration of single intravenous and oral doses of dolasetron mesylate 2.4 mg/kg in 18 healthy elderly subjects. Expressed as the dolasetron base, this dose was 1.8 mg/kg. Dolasetron was rapidly metabolized to the reduced metabolite, which appeared in plasma within 10 minutes after intravenous or oral administration. The mean half-life (t1/2) of dolasetron was 0.24 hours after intravenous administration and 0.50 hours after oral administration. The pharmacokinetic parameters of the reduced metabolite were similar after intravenous and oral administration. The apparent absolute bioavailability of the reduced metabolite was 89%, and it had an elimination t1/2 of approximately 7 hours and an apparent volume of distribution (Vd beta) of 4.69 L/kg. Dolasetron was not detected in urine. Metabolites were excreted in urine almost completely within 24 hours of administration. The primary metabolite detected in urine was the (+)-enantiomer of the reduced metabolite, which accounted for 25.35% (+/- 7.79%) and 18.88% (+/- 7.65%) of the intravenous and oral doses, respectively. Hydroxylated metabolites accounted for 5% or less of the total dose via either route. The pharmacokinetics of the reduced metabolite after single intravenous or oral doses in elderly volunteers were consistent with pharmacokinetics observed in both young healthy men and cancer patients receiving high-dose cisplatin chemotherapy. Dosage adjustments of dolasetron mesylate on the basis of age do not appear to be necessary.
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PMID:Pharmacokinetics of single intravenous and oral doses of dolasetron mesylate in healthy elderly volunteers. 893 Jul 77


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