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)

Chemotherapy-induced emesis is one of the major problems in the treatment of oncologic patients. Recently, a novel class of compounds, the selective 5HT3 receptor antagonists, has been introduced, achieving a dramatic improvement in the control of emesis. The absence of extrapyramidal side effects adds to their safety and good tolerability. The Authors herein analyse their experience on 269 cycles of chemotherapy in 47 patients treated for gynaecological and breast malignancies, with particular regard to adverse events such as headache. Their most frequent side-effects are headache and constipation, that are usually mild and self-limiting. Nevertheless, in some cases, severe, rebel headache has been reported, leading in our experience in 6.4% of cases to discontinuation of the antiemetic regimen. A previous history of recurrent or severe headache or migraine is not correlated with the occurrence of ondansetron-induced headache, as severe headache occurred after ondansetron only in 28.4% of the patients with positive anamnesis, and 70% of the patients that experienced had never suffered from severe headache before. In those patients complaining of severe headache, the Authors suggest an antiemetic association, with a loading dose of ondansetron i.v., followed by metoclopramide i.m. orally for the following days.
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PMID:Ondansetron-induced headache. Our experience in gynecological cancer. 766 68

Ondansetron is a selective 5-HT3 receptor antagonist which has previously been reported in the Journal to be a promising new agent for use as prophylaxis against nausea and vomiting caused by chemotherapy and radiotherapy. Since the publication of this original review, further studies have been published that show ondansetron to be an effective antiemetic agent in patients receiving chemotherapy and radiotherapy. Several studies have shown ondansetron to be a more effective antiemetic agent than high-dose metoclopramide in patients with emesis induced by high- and low-dose cisplatin treatment, and noncisplatin chemotherapy-induced emesis. The drug as mono-therapy does not appear to offer any advantage over alternative therapies against delayed high-dose cisplatin-induced nausea and vomiting; however, extremely limited data suggest that ondansetron plus dexamethasone may be useful in this indication. Trials have shown combination therapy with ondansetron and dexamethasone to be significantly more effective than both ondansetron monotherapy and a standard antiemetic regimen comprising metoclopramide, dexamethasone and diphenhydramine against acute high-dose cisplatin-induced emesis. Results from a number of small scale trials suggest that ondansetron may be an effective treatment for chemotherapy-induced emesis refractory to conventional antiemetic therapy. Ondansetron also appears to be more effective against refractory emesis induced by noncisplatin chemotherapy than that induced by cisplatin chemotherapy. Several trials have shown ondansetron to be more effective than placebo as prophylaxis against postoperative nausea and vomiting; a further trial has shown single-dose ondansetron to be significantly more effective than single-dose droperidol or metoclopramide in this indication. In addition, several trials have shown ondansetron to be more effective than placebo as treatment for nausea and vomiting that has commenced postoperatively. The overall incidence of adverse events in ondansetron recipients during chemotherapy-induced emesis studies was 36%. Headache and constipation are the most common adverse events during ondansetron therapy. Thus, recent data affirms the efficacy of ondansetron in the treatment of acute chemotherapy-induced nausea and vomiting and shows it to be especially efficacious when combined with dexamethasone. It appears that the drug will also have a substantial role in the prophylaxis and treatment of postoperative nausea and vomiting.
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PMID:Ondansetron. An update of its therapeutic use in chemotherapy-induced and postoperative nausea and vomiting. 769

The selective 5HT3 antagonist tropisetron was studied in 91 outpatients meeting DSM-III criteria for Generalized Anxiety Disorder. Following a placebo washout period of up to 1 week, one of three active treatments (tropisetron 0.5 mg, 5 mg, or 25 mg daily) or placebo was given for a further 3 weeks. After 7 days treatment termination rates due to inefficacy showed a statistically significant dose-related therapeutic effect of tropisetron. Similar effects were seen on the Hopkins Symptom Check List total score and the Global Impression Scale. The Hamilton Anxiety Scale showed a similar trend which, however, failed to reach statistical significance. At day 21 tropisetron showed significant dose-dependent effects on all anxiety-related outcome measures. The incidence of adverse events was low and the severity generally mild. Most frequent complaints were headache, nausea, constipation and nervousness. Laboratory tests and physical examination performed at baseline and study end showed no significant treatment effects.
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PMID:A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. 787 Oct 1

The efficacy of Granisetron, a new and selective 5HT3-receptor-antagonist in the treatment of cytostatic induced emesis, was tested in the department of gynaecology and obstetrics of the University of Essen on 77 patients. The patients received cytostatic drugs with a high emetogenic potency (for example cisplatin) or with a moderately high emetogenic potency (for example cyclophosphamide). We were able to demonstrate the high antiemetic efficacy of Granisetron. We had in 63% of the cases a "complete response" during the first 24 h after the chemotherapy and a "complete response" of 60% for the "delayed emesis". The observed adverse reactions such as constipation and headache were easily solved with standard laxatives or standard analgesics. Because of the high efficacy of Granisetron, which was combined with a low rate of side effects, it was possible to give to all the 77 patients the complete and necessary chemotherapy, so that no patient refused to receive the chemotherapy just because of nausea or emesis. The use of Granisetron is therefore a major step forward in the care of patients receiving chemotherapy because nausea and emesis can be treated effectively.
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PMID:[Granisetron, a new and potent antiemetic for treatment of cytostatic drug-induced vomiting in gynecological malignancies]. 815 Feb 51

Tropisetron is a novel, potent and highly selective 5-HT3 receptor antagonist, which is active in the treatment of nausea and vomiting induced by highly emetogenic chemotherapeutic drugs such as cisplatin. Tropisetron selectively blocks the excitation of the presynaptic 5-HT receptors of the peripheral neurones involved in the emetic reflex, and may have other direct actions in the CNS on 5-HT3 receptors, mediating the actions of vagal inputs to the area postrema. Toxicological studies show that tropisetron is generally well tolerated by all animal species investigated and no specific organ toxicity was observed, other than slight loss of body weight development. In man, tropisetron metabolism is linked to the cytochrome P-450 2D6 isoenzyme system, which determines the polymorphism of debrisoquine/sparteine metabolism. As a result, there are phenotypical populations of extensive and poor metabolizers. The two main adverse events in human volunteer tolerability studies with tropisetron were headache and constipation. These adverse events tended to be slightly more intense and to last longer in poor metabolizers, compared with extensive metabolizers. Tropisetron had similar pharmacokinetic characteristics in elderly patients and renal patients, compared with healthy subjects. From a toxicological and pharmacokinetic point of view, therefore, daily doses of 5 mg tropisetron can be administered to both poor and extensive metabolizers, as well as to special populations, without any particular precautions.
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PMID:Pharmacology, toxicology and human pharmacokinetics of tropisetron. 836 93

An open, two-armed, multicentre trial was conducted in 231 patients with malignant disease who had previously failed to respond to conventional antiemetic treatment for the prevention of chemotherapy-induced nausea and vomiting. Patients were randomized to receive either tropisetron (5 mg/day; n = 115) or a standard antiemetic therapy, which was considered optimal for each individual but did not include a 5-HT3 receptor antagonist (n = 116). Acute vomiting on Day 1 was controlled in 60 (52%) tropisetron patients, compared with only 29 (25%) patients receiving optimal standard therapy (p < 0.001). Acute nausea was completely inhibited in 37 (32%) tropisetron patients, compared with 22 (19%) patients on optimal standard therapy (p < 0.05). On Day 1, delayed vomiting was also significantly better prevented by tropisetron (p < 0.001). Side effects from tropisetron (headache and constipation) were mild, and no extrapyramidal symptoms were observed in any tropisetron patients, in contrast, to 14 (13%) patients in the 'optimal standard' group. In conclusion, in cases of acute nausea and vomiting it is more effective to switch refractory patients to tropisetron rather than attempt to optimize the dose of standard antiemetic therapy. For delayed nausea and vomiting, combination antiemetic therapy, with differing types of receptor antagonism and corticosteroids may provide the best way forward. Such studies are in progress.
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PMID:Tropisetron in the prevention of chemotherapy-induced nausea and vomiting in patients responding poorly to previous conventional antiemetic therapy. 836 95

An open, non-comparative, Nordic multicenter study was performed during 1991-1992 to evaluate the new 5-HT3 receptor antagonist tropisetron, as an antiemetic agent in various types of cancer chemotherapy. More than 600 patients were recruited from 16 cancer centers in Sweden, Finland and Denmark. In this report an interim analysis on 231 patients is presented. Gynecological cancers (61%), lung cancer (14%) and breast cancer (7%), were the main diagnoses. In 118 of 231 patients (51%) prior experience of chemotherapy was documented. In 91 patients (39%) cisplatin was part of the cytostatic regimen. Carboplatin (27%), doxorubicin (32%), epidoxorubicin (18%) were also frequently included. In all, 18 cytostatic agents were studied. The median number of courses studied was 3.3 (range 1-15). Overall 153 of 231 patients (67%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting (Days 2-6) were completely controlled in 45%-72%. Treatment efficacy remained stable (57%-89%) over 10 consecutive courses of chemotherapy. For non-cisplatin regimens complete protection was achieved in 78% compared with 51% for cisplatin-regimens (p < 0.0001). Patients with no prior experience of chemotherapy had greater control of acute nausea and vomiting (73%) than patients treated before (61%) in the first course, but not in subsequent courses. There were no such differences in control of delayed nausea and vomiting between chemotherapy-naive and previously treated patients. Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%-36% of the cases during long-term follow-up. Headache (16%) and constipation (5%) were most frequent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tropisetron in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. 836 99

Ondansetron, a highly selective 5-HT3 receptor antagonist, is available in an intravenous (IV) formulation and tables, but syrup would be particularly useful in children. As chemotherapy can affect taste perceptions, this study was undertaken to determine the preference between two flavors of ondansetron syrup in children undergoing chemotherapy. Fifty-nine children, randomized into a multicenter, double-blind, crossover study, each received 5 mg/m2 of IV ondansetron daily before chemotherapy. The syrup was then randomly given in two doses, one of each flavor, strawberry and grape, 30 minutes apart. The preference was assessed 30 minutes after the second dose of syrup had been administered. Taste was assessed by the child against a panel of five faces. Of those children expressing any preference, 70% preferred the strawberry flavor. Overall, 59% of children preferred the strawberry flavor, whilst 25% preferred grape (P = 0.005) and 15% expressed no preference. The only adverse event assessed as drug related by the investigator was constipation, which occurred in one patient. In conclusion, a strong preference was found for the strawberry formulation. The ondansetron syrup was safe and well tolerated.
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PMID:A randomized study of ondansetron syrup in children: evaluation of taste acceptability and tolerance. 872 Oct 40

Intravenous 5-hydroxytryptamine3 (5-HT3) receptor antagonists are now established antiemetics in the treatment of chemotherapy-induced emesis. For optimal convenience and acceptability, oral therapy is desirable. Retrospective comparisons indicate that oral granisetron may have an efficacy comparable with that of intravenous granisetron. Recent new data are available on the use of granisetron in the prophylaxis of acute emesis in randomized, double-masked trials. After moderately emetogenic chemotherapy, the optimal regimen appears to be 1 mg twice daily, although 2 mg once daily is equally effective. Oral granisetron is significantly superior to oral prochlorperazine. After high-dose cisplatin chemotherapy, oral granisetron is as effective as metoclopramide plus dexamethasone; the addition of dexamethasone further enhances its efficacy. Oral granisetron was well tolerated in all these trials. Headache and constipation were the most common adverse events, as has been reported for other 5-HT3 receptor antagonists. No randomized trials of oral-only tropisetron or dolasetron have yet been published.
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PMID:Comparative efficacy of oral and intravenous granisetron for the prevention of acute chemotherapy-induced emesis. 887 88

Efficacy and safety of the antiemetic agent Navoban (5HT3-receptor-antagonist Tropisetron) on cytostatic-induced emesis of breast cancers and gynecological cancers was tested in 28 female patients receiving a total of 127 chemotherapy courses containing high (cisplatin), moderate high (cyclophosphamid) or moderate (for example 5 FU) emetogenic cytostatic drugs. We studied antiemetic response rates of Navoban (5 mg/d) during the first 24 hours after administration of the chemotherapy as well as response rates of the "delayed nausea and emesis" (days 2-9 after chemotherapy). A complete response was observed in 103 chemotherapy courses (= 81.1%) during the first 24 hours after chemotherapy and in 93 courses (= 73.2%) for the "delayed emesis". Treatment failures (more than 5 vomiting episodes) during the first 24 hours were present in four courses and for the "delayed emesis" in 11 courses. The side effects of Navoban such as constipation, headache or tiredness were minimum. Therefore no patient refused to receive the necessary chemotherapy. Navoban is, with its single dose application, an effective therapeutic drug for the prevention of nausea and emesis in patients receiving a chemotherapy.
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PMID:[Effectiveness and tolerance of Navoban (5HT3-receptor antagonist tropisetron) in prevention of cytostatic drug-induced nausea and vomiting in patients with breast carcinomas and gynecological malignancies]. 890 Jun 4


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