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

Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT3 receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies.
Bull Cancer Radiother 1994
PMID:[Efficacy of ondansetron in radiation-induced nausea and vomiting: review of the literature]. 770 1

Most tests used for the screening of 5-HT3 receptor antagonists are not completely specific but they give satisfactory results when they are used in battery. In cancer chemotherapy and radiotherapy, 5-HT3 receptor antagonists are very active against acute emesis but delayed and anticipatory vomiting remains difficult to cure. Potential activities of 5-HT3 receptor antagonists as neuroleptics, anxiolytics and agents useful against dependence and cognitive disorders pose some problems in animal psychopharmacology and remain to be clinically validated.
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PMID:[Current status of the activity of 5-HT3 receptor antagonists in animal pharmacology]. 774 22

The cardiac effect of granisetron, a selective 5-hydroxytryptamine3 receptor antagonist, on 12 patients with bone and soft-tissue sarcomas treated by cytotoxic chemotherapy consisting of multiple courses was examined. Of the 12 patients, 4 showed significant electrocardiographical changes, including sinus bradycardia, integral change of P-waves, junctional escape beat, and atrioventricular (AV) block with Wenckebach phenomenon, indicating stimulatory regulation of the vagus nerve. These changes were observed in each patient after several courses of chemotherapy but not in the first course. There was no correlation between the electrocardiographical changes and the chemotherapeutic agents used or the type of tumor present. A patient with osteosarcoma showed persistent bradycardia in three courses, all protocols of which contained high-dose methotrexate. From these findings we conclude that the cardiac responses may be due to stimulated activity of the vagal efferent nerve, which is regulated reflexly by afferent nerve activity suppressed by granisetron. On the other hand, the antiemetic efficacy of granisetron was satisfactory. These results suggest that careful observation of the heart is necessary when granisetron is used, especially for chemotherapy consisting of repeated multiple courses.
Cancer Chemother Pharmacol 1995
PMID:Possible cardiac side effects of granisetron, an antiemetic agent, in patients with bone and soft-tissue sarcomas receiving cytotoxic chemotherapy. 782 69

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)
Support Care Cancer 1994 Nov
PMID:Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting--the Nordic experience. 785 34

We investigated the potential of cross-over to the serotonin receptor (5HT3) antagonist ondansetron after protection failure with tropisetron. Several cases of complete protection were observed. These limited data suggest that there is an indication for retreatment with a different 5HT3 antagonist after an initial failure to another and also stress the need and relevance for comparative studies between 5HT3 antagonists.
J Cancer Res Clin Oncol 1995
PMID:Possible lack of full cross-resistance of 5HT3 antagonists; a pilot study. 788 75

The pharmacology of 5-HT and the classification of 5-HT receptors have become increasingly complex. However, recent advances have produced a new nomenclature system for 5-HT receptors. 5-HT3 receptors are neuronal receptors coupled directly to cation channels. Recently, many selective 5-HT3-receptor antagonists including tropisetron, zacopride, ondansetron, granisetron, zatosetron, nazasetron, YM060 and YM114 (KAE-393) have been developed. Many actions attributable to the 5-HT3-receptor have been described in both the peripheral and central nervous systems, and clinical trials are already showing the potential use of these 5-HT3 receptor antagonists in a number of disorders of the gastrointestinal tract and central nervous system, such as nausea and vomiting induced by cancer chemotherapy, anxiety, depression, schizophrenia and migraine. In addition, endogenous 5-HT is suggested to be one of the substances that mediate stress-induced responses in gastrointestinal function, i.e., increase in fecal pellet output and diarrhea. Moreover, YM060, YM114 (KAE-393) and granisetron have been reported to inhibit restraint stress- and 5-HT-induced increases in fecal pellet output and diarrhea in rats and mice, indicating that endogenous 5-HT may mediate stress-induced changes in bowel function through the 5-HT3 receptor. Therefore, 5-HT3-receptor antagonists are new therapeutic drugs for stress-induced gastrointestinal dysfunctions like irritable bowel syndrome (IBS).
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PMID:[Serotonin (5-HT)3 receptors: antagonists and their pharmacological profiles]. 795 7

Ondansetron is a competitive serotonin 5-HT3 receptor blocker that has proved useful in the prevention of emesis due to cisplatin and other cancer chemotherapeutic agents. In a randomized, open-label, crossover study in 24 healthy male subjects, the relative bioavailability of a single 8-mg tablet was compared with that of an 8-mg solution using the two one-sided t-tests. The tablet and solution formulations were bioequivalent, as confirmed by similarities in mean Cmax (26.3 vs 27.7 ng/mL), Tmax (1.79 vs 1.70 h), and AUC (166.0 vs 167.3 ng.h/mL) values. In another randomized, open-label, crossover study in 12 healthy male subjects, the bioavailability of an 8-mg ondansetron tablet administered 5 min after a standard meal was slightly but significantly greater than in fasted subjects, as indicated by comparative mean AUC values [201.4 ng.h/mL (fed) vs 172.5 ng.h/mL (fasted)]. Coadministration of a magnesium hydroxide/aluminum hydroxide antacid did not affect the bioavailability of the ondansetron tablet.
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PMID:Ondansetron absorption in adults: effect of dosage form, food, and antacids. 796 57

Considerable progress has been made in the development of means to limit nausea and vomiting arising from cancer chemotherapy. A number of key conceptual advances in the last decade have been critically important. these include recognition of the value of combination antiemetic therapy, identification of important patient- and treatment-related factors predictive of emesis, and appreciation of the importance of serotonin (5-HT) in the pathophysiology of emesis and the value of selective antagonists of the type-3 serotonin receptor. Comparative trials of the 5-HT3 receptor antagonists and classic antiemetic agents have helped define optimal antiemetic approaches in a number of settings. A combination of a 5-HT3 antagonist and dexamethasone is the treatment of choice for patients receiving single- and multiple-day cisplatin. The 5-HT3 antagonists are also effective agents with noncisplatin chemotherapy. Clear-cut superiority to classic antiemetics such as dexamethasone has not been consistently demonstrated, however. Results with the 5-HT3 antagonists in cisplatin-induced delayed emesis have been disappointing to date. The results of ongoing prospective trials should define their role more clearly. At present a combination of metoclopramide and dexamethasone is the treatment of choice in this setting. Results of trials comparing 5-HT3 antagonists are beginning to emerge. Available information suggests no clinically relevant differences in antiemetic efficacy between these agents. Many questions regarding the optimal use of the 5-HT3 antagonists and their integration into clinical practice remain unanswered and are the appropriate focus for additional study.
Support Care Cancer 1994 Sep
PMID:Treatment of chemotherapy-induced emesis in the 1990s: impact of the 5-HT3 receptor antagonists. 800 Jul 24

The serotonin-receptor (5-HT3) antagonists combined with dexamethasone are considered the antiemetic therapy of choice in the prevention of cisplatin-induced emesis. As there are now several compounds on the market, the dilemma of preference is particularly relevant. In preclinical studies some differences among the three marketed drugs (ondansetron, granisetron and tropisetron) have emerged. In particular, tropisetron and granisetron have a greater potency and duration of action and seem to have a greater selectivity toward the 5-HT3 receptor with respect to ondansetron. Furthermore, while with tropisetron and granisetron there is a linear dose/response relationship, this does not seem to be the case for ondansetron. These preclinical differences, however, do not seem to correlate with the clinical antiemetic activity of these compounds. In fact, although the number of comparative studies is small, with all of them presenting several shortcomings (small number of patients, not blinded studies, no association with steroids, sponsored trials), it seems that the antiemetic activity and tolerability of ondansetron, granisetron and tropisetron is very similar. If these data are confirmed, the least expensive of the 5-HT3 antagonists should be the drug of choice. We feel, however, that the answer to this rather difficult question of choice will come from very large, independent, methodologically correct studies designed to show small but clinically significant differences (i.e., less than 10% in complete protection from emesis). These trials, which require about 1000-1500 patients, are ongoing and the one carried out as a multicenter study by the Italian Group for Antiemetic Research is close to conclusion.
Support Care Cancer 1994 Sep
PMID:Are there differences among the serotonin antagonists? 800 Jul 25


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