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

The most frequent side effects of chemotherapy are nausea and vomiting. This issue is a clinical analysis of the protective effect of a 5HT3 antagonist (Navoban-R; Sandoz Pharma Ltd., Basel, Switzerland) against chemotherapy--induced emesis (especially with the most emetic cytostatics--cisplatin and dacarbazine). In the first day of treatment, Navoban demonstrates a control of emesis for 75% of patients and in the following days for 80% of patients. The nausea is more frequent than vomiting. The most frequent side effects of Navoban were: headache (75% of patients), dizziness (62% of patients) and tiredness (50% of patients). This drug is a good protective against chemotherapy induce emesis and is very easy to administer.
 ...
PMID:[The antiemetic action of tropisetron (Navoban) in the cytostatic treatment of neoplastic diseases]. 945 57

Insight into the pathophysiology of antineoplastic therapy-induced nausea and vomiting led to the development of the serotonin 5-HT3 receptor antagonists as the most potent class of antiemetic agents. Among those which have been investigated are ondansetron, granisetron, tropisetron and dolasetron. A risk-benefit analysis of these drugs must not only account for the modest clinical differences in efficacy and tolerability, but also should include such issues as ease of use, route of administration, dosage considerations and patient preference. Pharmacokinetic and preclinical studies reveal distinctions among these antiemetics, but, overall, these distinctions do not translate in to clinically significant differences. In clinical trials, the most widely studied members of the 5-HT3 receptor antagonists are granisetron and ondansetron, which have been found to possess equivalent antiemetic efficacy. Dolasetron and tropisetron are also available, and some randomised trials have also documented their similar antiemetic activity, depending on the doses and schedules used. The equivalent efficacy of oral granisetron 2 mg versus intravenous ondansetron 32 mg has recently been demonstrated in prospective randomised clinical trials in patients receiving either highly emetogenic or moderately emetogenic antineoplastic therapy. The utilisation and efficacy of oral ondansetron and dolasetron in patients receiving moderately emetogenic antineoplastic therapy has also been documented. This review offers a brief overview of the pharmacokinetic and preclinical research on the 5-HT3 antagonists, a review of the comparative clinical trials of the major members of this class and a summary risk-benefit assessment that considers clinical applicability and cost, as well as efficacy and safety.
 ...
PMID:A risk-benefit assessment of serotonin 5-HT3 receptor antagonists in antineoplastic therapy-induced emesis. 946 87

We conducted an evaluation of the usefulness of antiemetics (5-Hydroxy-tryptamine 3 receptor antagonism, 5HT3RA) combined with diazepam for delayed nausea and vomiting due to anticancer agents in 17 patients with various malignancies (such as lung Ca, breast Ca, esophagus Ca, gastric Ca, colon Ca, and non Hodgkin's disease) for whom chemotherapy was performed with different regimens in the Dept. of Oncologic Chemotherapy, People's Hospital, Beijing Medical University. Antiemetics (5HT3RA) combined with diazepam were given only to cases that had symptoms of nausea and vomiting induced by anticancer agents in the 1st course and invalidity with antiemetics (5HT3RA) alone in this study. Antiemetic (5HT3RA) agents + Dexamethasone were dosed before chemotherapy and also diazepam 5 mg orally after 24 hours (namely, when nausea was observed). Nausea was reduced and vomiting decreased after the antiemetic treatment with 5HT3RA + Dexamethasone and diazepam. These results indicated that 5HT3RA and diazepam combination therapies were more effective than 5HT3 RA + Dexamethasone alone for delayed nausea and vomiting. Further, the antiemetics had characters that a short adminiter time, few times and a take not over dose. The only side effect related to this antiemetic therapy was light somnolence. Antiemetics combined with diazepam might be a useful therapy against delayed nausea and vomiting induced by anticancer agents.
 ...
PMID:[Effect of diazepam on delayed nausea and vomiting caused by anticancer agents]. 949 33

In the mid-1980s it was discovered that serotonin (5-hydroxytryptamine; 5-HT) was at least partially responsible for producing chemotherapy-induced nausea and vomiting. It was therefore realised that serotonin receptor blockade with serotonin 5-HT3 receptor antagonists could inhibit chemotherapy-induced nausea and vomiting. 5-HT3 antagonists have different chemical structures and receptor binding affinity. Granisetron, dolasetron and its major metabolite are pure 5-HT3 antagonists, while ondansetron and tropisetron are weak antagonists at the 5-HT4 receptor. Ondansetron has also been demonstrated to bind at other serotonin receptors and to the opioid mu receptor. The half-lives of granisetron, tropisetron and the active metabolite of dolasetron are 2 to 3 times longer than that of ondansetron. These observations initially suggested that more frequent ondansetron administration would be required; however, it has now been shown that receptor blockade does not correlate with elimination half-life and all 5-HT3 antagonists can be effectively administered once daily. Clinical trials have been conducted that directly compare the 5-HT3 antagonists. To compare these studies, it is necessary to assess trial design, including known risk factors for the development of chemotherapy-induced nausea and vomiting, and response criteria. Stratification for risk factors, use of strict efficacy criteria and randomisation to a blinded trial using an appropriate comparative regimen are essential for a well designed antiemetic trial. Comparative clinical trials using various doses, routes and regimens of administration have been conducted with 5-HT3 antagonists. Despite some trial design shortcomings, most of the studies show equal efficacy between the agents, especially in moderately emetogenic chemotherapy and mild, infrequently occurring adverse effects. The addition of steroids also appears to improve outcome. However, since many doses and regimens of ondansetron were used, further study is needed to determine the optimal regimen. The efficacy of 5-HT3 antagonists in controlling delayed nausea and vomiting from chemotherapy is less well studied. Further, there is no good scientific rationale for the use of 5-HT3 antagonists in controlling delayed nausea and vomiting since serotonin has not been shown to be released during the delayed phase. In fact, most studies show no benefit or modest benefit of 5-HT3 antagonists over placebo. Because the 5-HT3 antagonists perform similarly in the clinical setting, pharmacological differences do not seem to translate into therapeutic differences. There is also no appreciable difference in the incidence or severity of adverse effects among the 5-HT3 antagonists. Determination of clinical use may then be driven by cost.
 ...
PMID:5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. 950 40

At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.) identified chemotherapy-induced nausea and vomiting as one of the most distressing adverse events, and decided to plan and execute clinical trials on antiemetics in order to reduce this negative impact on patients. Therefore, some consecutive double-blind randomized trials were conducted on cisplatin-treated patients. The first was a dose-finding study on four different high-doses of domperidone, followed by a study comparing two different high-doses of metoclopramide, and a study comparing the addition of a corticosteroid to high-dose metoclopramide with respect to metoclopramide alone. Finally, a study demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2) plus dexamethasone and diphenhydramine was significantly superior with respect to a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was carried out. With the introduction of the 5-HT3 receptor antagonists the interest for antiemetic therapy increased and other Italian gynecological and medical oncology centres became involved in the antiemetic research. The Italian Group for Antiemetic Research was formed in 90's and its first study demonstrated the superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone with respect to the standard three drug combination of high doses of metoclopramide in the prevention of cisplatin-induced acute emesis. In the following years, the Group contributed to the identification of the best antiemetic prophylaxis for acute emesis induced by moderately emetogenic chemotherapy, and for delayed emesis induced by cisplatin. Also a drug utilization review on antiemetics in clinical practice has recently been carried out. Today, the interest of the Group is concentrated in studying the optimal antiemetic prophylaxis for delayed emesis induced by moderately emetogenic chemotherapy. The rules always followed by the Italian Group for Antiemetic Research are: --complete independence of judgement on the efficacy and the tolerability of antiemetic drugs from the pharmaceutical companies; --priority of ethical problems in designing clinical trials; --strict adherence to the methodological problems of antiemetic research and--complete autonomy concerning the study planned, the data computerization and the data elaboration. In the last twelve years approximately 70 Italian centres have enrolled their patients into the studies of the Italian Group for Antiemetic Research.
 ...
PMID:[Research on antiemetics: an Italian model of success]. 961 77

Only a few studies have been carried out specifically on the prevention of nausea and vomiting in children receiving chemotherapy. In these patients older antiemetic drugs such as metoclopramide and phenothiazines had moderate efficacy and induced significant side effects, especially marked sedation and extrapyramidal reactions. In comparative trials the 5-HT3 receptor antagonists have shown better efficacy and tolerability than chlorpromazine or metoclopramide combined with dexamethasone. The combination of a 5-HT3 receptor antagonist plus dexamethasone is superior to a 5-HT3 receptor antagonist alone and should be the standard antiemetic prophylaxis in all paediatric patients receiving highly or moderately emetogenic chemotherapy. The optimal dose and scheduling of these antiemetic drugs need to be studied, as well as the antiemetic efficacy, in the prevention of chemotherapy-induced delayed and anticipatory emesis in children.
 ...
PMID:Optimal selection of antiemetics in children receiving cancer chemotherapy. 962 72

The treatment of nausea and vomiting in patients receiving high doses of irradiation and/or chemotherapeutic agents as preparation for hematopoietic stem cell transplantation is discussed. Such patients have very high rates of both early and delayed emesis. Based on the available evidence it is recommended that 5-HT3 receptor antagonists be used to combat emesis in this setting. Continued research is also required to define the optimal antiemetic strategy for these patients.
 ...
PMID:Antiemetic strategies for high-dose chemoradiotherapy-induced nausea and vomiting. 962 75

A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and 27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes) occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each agent (P = NS). However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory.
 ...
PMID:Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental patients: a randomized crossover study. 963 49

The ability of 2,2,2-trichloroethanol (TCE) and related alcohols to modify the 5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated cervical vagus nerve were investigated by extracellular electrophysiological recording using the 'grease gap' technique. TCE at millimolar concentrations increased the magnitude of the 5-HT3 receptor-mediated depolarisations of the rat vagus nerve by a number of agonists (5-HT, phenylbiguanide (PBG), quipazine). Concentration response curves generated for the 5-HT3 receptor agonists. 5-HT and PBG, in the absence and presence of TCE (5 mM) indicated that the potentiation in agonist-induced depolarisation was due to an increase in both agonist potency and apparent efficacy. Following apparent complete 5-HT3 receptor desensitisation (induced by either 5-HT or PBG; 100 microM for 90 min), application of TCE (5 mM) in the continued presence of either agonist induced a depolarisation of the vagus nerve. In addition to TCE, a number of related alcohols (tribromoethanol, isopentanol and 5-chloropentanol but not ethanol) at millimolar concentrations also potentiated depolarisation of the vagus nerve induced by 5-HT. Combined application of both TCE (0.1-20 mM) and isopentanol (20 mM) indicated that the potentiation of the 5-HT3 receptor-mediated depolarisation by these alcohols was not additive. The present studies indicate that the 5-HT3 receptor expressed on the cervical vagus nerve is susceptible to allosteric modulation by a number of alcohols including the anaesthetic agent TCE. Such an interaction may have relevance to the nausea and vomiting experienced by some patients following recovery from general anaesthesia.
 ...
PMID:5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated vagus nerve: modulation by trichloroethanol and related alcohols. 972 27

Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials of dolasetron evaluating oral doses for prevention of chemotherapy-induced emesis, and intravenous doses for prevention and treatment of postoperative emesis have used a fixed milligram dose. To identify an appropriate intravenous fixed milligram dose for the prevention of chemotherapy-induced nausea and vomiting, this analysis was performed to derive efficacy results for fixed milligram doses from pooled results obtained with dosing based on body weight. Intravenous dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to fixed milligram doses based on weight. Fixed-dose groups were established at doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the midpoint between two dose groups were included in the lower dose group. Pooled results showed that the 100 mg intravenous dolasetron dose group (who received actual doses of 88-112 mg) produced the highest rate (53%) of complete response (0 emetic episodes and no rescue medication in the 24-h period following initiation of chemotherapy).
 ...
PMID:Rationale for the use of a single fixed intravenous dolasetron dose for the prevention of cisplatin-induced nausea and vomiting. Pooled analysis of 14 clinical trials. 977 66


<< Previous 1 2 3 4 5 6 7 8 9 10