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)

Ramosetron hydrochloride as a 5-HT3 receptor antagonist-type antiemetic, which was developed in Japan. It has an indole ring which is the mother nucleus of serotonin (5-HT) and a tetrahydrobenzimidazol radical. These components are linked by a carbonyl radical. It was reported in non-clinical studies that ramosetron hydrochloride exhibited more potent and sustained antagonistic activities against 5-HT3 receptors than existing 5-HT3 receptor antagonist-type antiemetics. It was also reported that ramosetron hydrochloride inhibited vomiting by anticancer drugs in a potent and sustained manner. The phase I trial was initiated in May, 1991. Phase II and phase III trials were then conducted in a total of 357 patients at 121 institutions in Japan. The symptoms targeted in these trials were nausea and vomiting induced by anticancer drugs, such as cisplatin. Based on the results of the phase II trial, it was recommended that ramosetron hydrochloride be infected once daily at a dose of 0.3 mg. In phase III trial, a placebo-controlled double-blind study and an open trial was performed. The utility of the drug seemed to be confirmed by the results of these studies. Ramosetron hydrochloride shown an efficacy rate of 79.8% (178/223 patients) against nausea and vomiting induced by anticancer drugs, such as cisplatin when administered at a dose of 0.3 mg. The efficacy rate was 85.1% (40/47 patients) when given at a dose of 0.3 mg before the administration of anticancer drugs, such as cisplatin. The incidence of adverse effects was 2.0% (7/352 patients). Main adverse effects reported were feeling of heat, headache, and heavy feeling in the head. These adverse effects were of no clinical importance.
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PMID:[A new antiemetic ramosetron hydrochloride]. 905 Nov 43

Chemotherapy-induced nausea and vomiting, two of the most distressing side-effects of cancer chemotherapy, have been the subject of a number of fundamental and clinical investigations. These have led to the development of a novel class of antiemetic agents, the 5-HT3 receptor antagonists. The pathophysiology of the emetic reflex and the clinical management of emesis are very complicated. Two experimental preclinical animal models are available (ferret and dog) and are particularly used to assess monochemotherapy as a single dose. Results are fairly good for acute nausea and vomiting. However, no optional animal model is available for the assessment of delayed and anticipated emesis. The clinical settings are so complex and variable that they preclude the development of an adequate model in all cases. It is also impossible to carry out clinical studies to assess each issue. Management of nausea and vomiting depends on the analysis by the physician of individual and drug-related parameters and on his own expertise. Scores can be assigned to each parameter and a decision tree can be elaborated to help the decision and improve the management of patients. The first goal is to obtain an optimal control of emesis from the very first cycle of chemotherapy in order to ensure good control during subsequent cycles.
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PMID:[Chemotherapy-induced nausea and vomiting: from experimentation to experience]. 911 65

Chemotherapy-induced emesis has a major adverse impact on patients undergoing therapy for various malignancies, and this has led to considerable research in this field. Most investigative efforts have concentrated on the acute phase of emesis that occurs within the first 24 hours after chemotherapy, and significant strides forward have been made with this problem. Better control of acute emesis with newer agents such as the serotonin 5-HT3 receptor antagonists has focused increasing attention on a second phase of nausea and vomiting, known as delayed emesis, which occurs more than 24 hours after chemotherapy. This delayed phase is often not as well controlled with the antiemetics that have proven effective in acute emesis, and contributes to the distress associated with emetogenic chemotherapy. Most of the available data on delayed emesis are based on studies with cisplatin-based regimens, with much less understanding of delayed nausea and vomiting induced by non-cisplatin-based chemotherapy. Nevertheless, it is evident that the patterns of delayed emesis associated with cisplatin and non-cisplatin chemotherapy have distinct differences. The control of delayed emesis, especially following cisplatin, remains a therapeutic challenge. Contributing to the lack of progress has been the absence of an experimental model to help in elucidating the pathophysiology of delayed emesis and in the evaluation of new therapeutic approaches. The combination of metoclopramide and dexamethasone, although superior to placebo in randomised trials, provides only moderate control of delayed emesis following high-dose cisplatin. The 5-HT3 receptor antagonists that are effective in the prevention of acute emesis with cisplatin have failed to make a major impact on the delayed phase. When combined with dexamethasone, these agents provide no additional benefit to that achieved using dexamethasone alone or dexamethasone combined with metoclopramide. With non-cisplatin chemotherapy, corticosteroids and 5-HT3 receptor antagonists are the most useful agents. Efforts are ongoing to identify more effective treatments for delayed emesis. One novel approach involves the blockade of substance P binding to neurokinin-1 (NK1) receptors. This article reviews what is currently known about chemotherapy-induced delayed emesis, with a focus on treatment strategies.
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PMID:Drug treatment of chemotherapy-induced delayed emesis. 911 14

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

Azasetron, a selective 5-HT3 receptor antagonist, has been previously shown to be highly effective in the prophylaxis of nausea and vomiting induced by anticancer drugs, and is widely used in the clinical setting in Japan. In order to improve the antiemetic effect of azasetron, we designed two treatment methods using this drug and compared the antiemetic effect of this method with that of standard bolus intravenous injection on nausea and vomiting associated with anticancer drug including 75 mg/m cisplatin (CDDP). The two-treatment group received an intravenous bolus injection of 5 mg azasetron before and 8 hours after the start of chemotherapy, and a standard group was given an intravenous bolus injection of 10 mg azasetron only once a day. The inhibitory effect on vomiting in the two-treatment group was significantly greater than those of the standard group on day 1 and 2 (p = 0.0458, p = 0.0273), and the inhibitory effect on nausea of the two-treatment group tended to be superior those of the bolus group on day 2 (p = 0.0533). No adverse effects were observed in either group of this study. From these data, the two-treatment approach was considered to be highly effective in prophylaxis of nausea and vomiting induced by anticancer drug.
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PMID:[Clinical effect of two azasetron treatment methods against nausea and vomiting induced by anticancer drugs including CDDP]. 917 May 25

In the past few years important progress in the prevention of chemotherapy-induced nausea and vomiting has been made mainly thanks to the introduction of the 5-HT3 receptor antagonists in clinical practice (ondansetron, granisetron, tropisetron). In the prevention of acute emesis induced by cisplatin, an intravenous combination of a 5-HT3 receptor antagonist plus single dose dexamethasone (20 mg) should be considered the treatment of choice. This is also the case in the prevention of acute emesis induced by moderately emetogenic chemotherapy (intravenous cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination), but high and repeated doses of dexamethasone should be used (8 mg intravenously plus 4 mg orally every 6 hours for four doses starting contemporarily to chemotherapy administration). Several-well conducted double-blind comparative studies among intravenously administered 5-HT3 receptor antagonists have been carried out. Almost all showed that they have identical antiemetic activity and tolerability. Therefore, the choice among 5-HT3 receptor antagonists should be based only on their acquisition cost in each country. In the prevention of delayed emesis (from day 2 to day 4) induced by cisplatin oral metoclopramide (0.5 mg/kg or 20 mg every 6 hours for four doses daily) and oral ondansetron (8 mg twice daily), both combined with dexamethasone, showed similar antiemetic efficacy. Metoclopramide plus dexamethasone should be considered the antiemetic regimen of choice due to its lower cost. Ondansetron plus dexamethasone is a valid alternative regimen that should be preferred in patients who not tolerate metoclopramide and in patients who suffer from acute vomiting. In the prevention of delayed emesis induced by moderately emetogenic chemotherapy oral dexamethasone or oral ondansetron showed a good antiemetic efficacy, but the results from a recently published study seem suggest the necessity to treat only patients who present acute vomiting or moderate-severe nausea. In fact, patients obtaining complete protection from vomiting and nausea (or at most mild acute nausea) have a very low incidence of delayed emesis.
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PMID:[Recent improvements in antiemetic therapy]. 923 27

Recently, granisetron (KYT), one of the 5-HT3 receptor antagonists, has been developed and proved to have a strong effect for cisplatin (CDDP)-induced emesis. The combination chemotherapy with CDDP and 5-fluorouracil (5-FU), which has great efficacy for head and neck cancer, induces nausea and vomiting as side effects. We compared the effects of KYT for CDDP plus 5-FU-induced emesis between two administration schedules. Forty patients were randomized to two groups. KYT was administered either on day 1 for twenty patients (Group A), or for consecutive 5 days in another twenty patients (Group B). Additional antiemetics were administered in thirteen patients in Group A and seven patients in Group B for severe nausea and vomiting even after KYT administration. The times of additional antiemetics administration were more frequent in Group B. The nausea score was statistically lower in Group B and the duration of nausea or vomiting was statistically longer in Group A. The frequency of vomiting was the same in the two groups on day 1, but it was controlled faster in Group B. Appetite loss was lower on day 7 in Group B. It was concluded that vomit and nausea were controlled better in Group B after day 4. Additional antiemetics were not effective, and 5 consecutive administrations of KYT for chemotherapy with CDDP plus 5-FU was effective for late emesis.
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PMID:[Comparison of effects between single vs five-day injection of granisetron for combination chemotherapy with cisplatin and 5-fluorouracil for head and neck cancer]. 923 62

Dolasetron (dolasetron mesilate) is a pseudopelletierine-derived 5-HT3 antagonist which has recently become available for clinical use. It is rapidly converted in vivo to its active major metabolite, hydrodolasetron, which appears to be largely responsible for its pharmacological activity. In clinical trials, single intravenous or oral doses of dolasetron were effective in preventing acute chemotherapy-induced nausea and vomiting (CINV). Intravenous doses of 1.8 mg/kg achieved complete suppression of vomiting in approximately 50% of patients receiving highly emetogenic cisplatin-containing chemotherapy and in approximately 60 to 80% of patients receiving moderately emetogenic chemotherapy. In the latter setting, oral doses of 200 mg achieved similar response rates. In comparative studies, intravenous dolasetron 1.8 mg/kg was as effective as intravenous granisetron 3 mg or ondansetron 32 mg after highly emetogenic chemotherapy, and oral dolasetron 200 mg was equivalent to multiple oral doses of ondansetron (3 or 4 doses of 8 mg) after moderately emetogenic chemotherapy. Dolasetron 1.8 mg/kg was superior to metoclopramide in preventing emesis induced by high dose cisplatin or by moderately emetogenic chemotherapy in high risk subgroups. Dolasetron has also shown efficacy in preventing radiotherapy-induced nausea and vomiting (RINV) in preliminary studies. Single intravenous or oral dolasetron doses ranging from 12.5 to 100 mg and 25 to 200 mg, respectively, were significantly more effective than placebo in preventing postoperative nausea and vomiting (PONV) in female surgical patients. A 50 mg intravenous dose was as effective in preventing PONV as ondansetron 4 mg in a mixed-gender group. Intravenously administered dolasetron was also effective in treating established PONV, although complete suppression of vomiting was achieved in < 40% of patients. Dolasetron has a tolerability profile characteristic of this class of compounds, with headache, dizziness and diarrhoea being the most commonly occurring adverse events in clinical trials. Diarrhoea is not thought to be related to dolasetron administration, being experienced mostly by patients receiving chemotherapy. Dolasetron and other 5-HT3 receptor antagonists have been associated with minor changes in ECG intervals, but these generally do not appear to be clinically important. Thus, available evidence suggests that dolasetron will provide an alternative to other 5-HT3 receptor antagonists for the management of CINV and PONV. Further studies are required to determine whether it offers any advantages over other agents in these settings and to determine the optimum dosage for preventing RINV.
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PMID:Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery. 925 83

In 1983, Coates conducted a survey that ranked the side-effects perceived by patients receiving chemotherapy in the order of their severity. Vomiting and nausea were found to be the two most distressing side-effects. They have an impact on quality of life and compliance with treatment. The development of 5HT3 antagonists has been a major step forward in the prevention and treatment of chemotherapy-induced nausea and vomiting. Presently, these antiemetics are routinely used as concomitant therapy in emetogenic chemotherapy regimens. The purpose of this study was to evaluate the impact of 5HT3 antagonists on patient perceptions of the side-effects of chemotherapy. Coates' survey was replicated in patients who received 5HT3 antagonists for acute nausea and vomiting resulting from emetogenic chemotherapy. Patients received the survey to identify those physical and non-physical side-effects that they attributed to chemotherapy and were asked to rank the five most distressing side-effects. Of the 197 patients who consented to take part in the study, 181 were evaluable. Nausea, hair loss and vomiting were described as the three most distressing side-effects of chemotherapy. Eighty per cent of all the patients actually experienced nausea and 57% experienced vomiting. Hair loss appeared to be more distressing to women (P < 0.001) but, in other aspects, gender, age and marital status did not influence the ranking of the three most distressing side-effects. Constipation was ranked as 6th and was not identified as a distressing side-effect in 1983. Nausea and vomiting remain to be the first and third most distressing side-effects of chemotherapy, even though the incidence and severity of acute nausea and vomiting are now significantly reduced.
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PMID:Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. 937 66

Lower hemibody radiotherapy is an effective palliative treatment for patients with wide-spread bone metastases, but is frequently associated with the unpleasant side effects of nausea and vomiting. Patients often require admission to hospital for at least an overnight stay, with its inevitable costs. This study has investigated the clinical efficacy and safety profile of ondansetron, a 5HT3 receptor antagonist, and compared it to a standard antiemetic combination, chlorpromazine and dexamethasone. Sixty-six patients were randomised to receive antiemetic prophylaxis with either oral ondansetron or a combination of chlorpromazine and dexamethasone (33 patients in each arm): 60 were treated with lower abdominal radiotherapy (8 Gy mid-plane dose) and 6 with radiotherapy to the upper lumbar spine (12.5 Gy incident dose). Patients were assessed for severity of nausea and vomiting and for whether they would use the same antiemetic again. Quality of life was assessed using the Functional Living Index Cancer (FLIC) and Functional Living Index Emesis (FLIE) quality-of-life questionnaires. A detailed cost-benefit analysis was also performed. Ondansetron scored highly as an antiemetic, being significantly better at controlling emesis on all four study days (P < 0.001) and significantly better at controlling nausea on day 1 (P < 0.001) than the standard combination of chlorpromazine and dexamethasone. Quality of life was better in the ondansetron-treated group, and ondansetron was found to be safe with no significant adverse effects. As a result, 98% of patients and investigators would use ondansetron again. Cost-benefit analysis revealed that, when complete control of emesis is the aim, ondansetron is not unduly expensive compared to the standard antiemetic regimen. As ondansetron was clearly effective in patients receiving hemibody irradiation it seems it would be prudent to adopt it for use in such patients routinely. The use of ondansetron would allow them to be treated as outpatients, with the attendant financial and psychosocial benefits of such an approach.
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PMID:Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy. 940 64


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