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)

Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the 'moderate' doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics.
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PMID:Ondansetron. Therapeutic use as an antiemetic. 171 61

Granisetron (BRL 43694) is a highly selective 5-HT3 receptor antagonist which possesses significant antiemetic activity, likely mediated through antagonism of 5-HT3 receptors on abdominal vagal afferents and possibly in or near the chemoreceptor trigger zone. Clinical trials in cancer patients demonstrate that, compared with placebo, granisetron significantly reduces the incidence of nausea and vomiting for 24 hours after administration of high-dose cisplatin. In large comparative trials, 70% of patients who received granisetron prior to cisplatin or other chemotherapy experienced complete inhibition of vomiting with little or no nausea for 24 hours after antineoplastic administration; these results were similar to those obtained with high-dose metoclopramide plus dexamethasone, and superior to a combination of chlorpromazine plus dexamethasone, or prochlorperazine plus dexamethasone, or methylprednisolone monotherapy. The most frequently reported adverse event associated with granisetron administration is headache which occurs in about 10 to 15% of patients while constipation, somnolence, diarrhoea and minor transient changes in blood pressure have been reported less frequently. Extrapyramidal effects, which can occur with high-dose metoclopramide and may be a limiting factor in its use, have not been noted with granisetron administration. Thus, granisetron is an effective, well tolerated and easily administered agent for the prophylaxis of nausea and vomiting induced by cancer chemotherapy which appears to be devoid of extrapyramidal side effects associated with metoclopramide. As a member of a new class of drugs, the selective 5-HT3 receptor antagonists, granisetron provides the medical oncologist with a new, potentially more acceptable antiemetic therapy.
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PMID:Granisetron. A review of its pharmacological properties and therapeutic use as an antiemetic. 172 76

Combinations of dopamine antagonists or high-dose metoclopramide with steroids can provide complete control of chemotherapy-related nausea and vomiting in up to 60-70% of patients undergoing high-dose cisplatin-based chemotherapy. High-dose metoclopramide probably acts as a 5-HT3 receptor antagonist, but because of its dopamine-receptor antagonism it is the cause of extrapyramidal side-effects. These compounds, and the agents used in combination with them, tend to cause sedation, an undesirable effect in the outpatient setting. Specific 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) give a similar control of chemotherapy related nausea and vomiting, with minimum side-effects. These drugs can cause headaches and constipation and some have been related to transient liver enzyme abnormalities in cancer patients; however, disease and chemotherapy might also be the cause of the enzyme anomalies. Combinations of 5-HT3 receptor antagonists with steroids may provide a very high degree of protection.
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PMID:Controlling emesis related to cancer therapy. 182 31

5-HT3 receptors have been the focus of much research during the last decade. They are characterised by being located on neurones both peripherally and centrally; 5-HT3 agonists cause a rapid depolarisation of the membrane potential which results from the opening of cation channels; the 5-HT3 response rapidly desensitizes. 5-HT3 receptors appear to have a modulatory role on other neurotransmitters. The identification of selective agonists and antagonists for this receptor type has allowed the discovery of several important new therapeutic applications. The use of 5-HT3 receptor antagonists in psychoactive illnesses is being explored clinically. In addition, ondansetron, a selective 5-HT3 receptor antagonist, is already being used to prevent the severe nausea and vomiting caused by cancer chemotherapy and radiotherapy. The pharmacological properties of 5-HT3 antagonists are discussed in this chapter.
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PMID:5-HT3 receptors and the therapeutic potential of 5-HT3 receptor antagonists. 184 Feb 27

Fifty six patients, with histologically confirmed cancer, who received highly emetogenic chemotherapy, were entered on a randomized double blind, low versus high dose, study of granisetron, a 5HT3 receptor antagonist. A single dose of intravenous granisetron protected the majority of patients from nausea and vomiting, 160 micrograms/kg was more effective than 40 micrograms/kg with no more side effects. Additional doses of granisetron conferred added benefit to patients who experienced breakthrough symptoms. Granisetron at a dose range of 40-240 micrograms/kg over a 24 hour period was well tolerated with the only side effect being mild headache.
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PMID:High versus low dose granisetron, a selective 5HT3 antagonist, for the prevention of chemotherapy-induced nausea and vomiting. 196 78

A total of 25 patients (5 groups of 5) were given single i.v. doses of 5, 10, 20, 40 and 60 mg MDL 72,222 (a 5-HT3 receptor antagonist) at 15 minutes before the commencement of a 24-h cisplatin infusion (total dose, 120-200 mg) to determine the efficacy and safety of the former in the prevention of nausea and vomiting associated with such chemotherapy. All patients completed the study. The time to onset of vomiting was significantly correlated with dose. All patients vomited following doses of 5 and 10 mg (range, 1-6 episodes), with onset being noted at 5-8 h. At the 20-mg level, only one episode of vomiting was observed in 3/5 patients, with onset being observed at 18-22 h. Following doses of 40 and 60 mg, 3/10 patients did not vomit; in the remaining patients the number of episodes ranged from 1 to 6, but a significant increase occurred in the time to onset of symptoms. At the higher doses, nausea tended to be milder in nature both at onset and at the time of maximal severity. A similar dose-effect trend was seen in the time to onset of the maximal severity of nausea. The time to and requirement for escape medication was similarly extended at doses of greater than or equal to 20 mg MDL 72,222. Pain at the injection site in one patient was the only unwanted effect associated with MDL 72,222. The results suggest that the i.v. injection of 20 mg MDL 72,222 should be further explored in the control of nausea and vomiting associated with cisplatin administration.
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PMID:A single-dose-finding study of the antiemetic effect and associated plasma levels of MDL 72222 in patients receiving cisplatin. 201 17

Recent advances in the understanding of emesis have resulted in the development of serotonin 3 receptor antagonists. The careful use of these drugs and other conventional antiemetic agents can substantially reduce the nausea and vomiting associated with chemotherapy and improve the quality of life for cancer patients undergoing treatment.
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PMID:Management of vomiting associated with cytotoxic therapy. 201 89

A total of 33 patients with myeloma receiving treatment with high-dose melphalan (140-200 mg/m2 i.v.) were given the 5HT3 antagonist Ondansetron (Glaxo) as an antiemetic. In 42% of patients, emetic episodes were either abolished (15%) or reduced to two or less (27%). Efficacy was not related to scheduling (two regimens) or total dose. No sedative or other significant side effects were seen. Ondansetron is a highly effective non-sedative antiemetic that justifies further assessment in combination with other antiemetics in patients receiving cytotoxic drugs associated with the production of severe nausea and vomiting.
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PMID:Ondansetron--a new safe and effective antiemetic in patients receiving high-dose melphalan. 213 64

In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.
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PMID:[Gastrointestinal toxicity induced by anticancer drugs--including new antiemetic drugs]. 214 Apr 98

Ondansetron, a 5HT3 antagonist, was given to 20 children aged 4 to 18 years who were undergoing treatment with the Australian and New Zealand Childhood Cancer Study Group Acute Lymphocytic Leukaemia (ALL) Study V Protocol. The study was open, dose ranging, and noncomparative, and designed to evaluate safety and efficacy of ondansetron in preventing nausea and vomiting caused by cyclophosphamide intravenous (IV) 1,000 mg/m2 day 1, and cytarabine IV subcutaneously (SC) 75 mg/m2 on days 2 to 5. Ten patients were given ondansetron 5 mg/m2 IV (group A) and subsequently another 10 patients were given ondansetron 3 mg/m2 IV (group B). Oral ondansetron was given for 14 doses, at the same dosage for both groups, commencing simultaneously with the IV infusion and continuing at 8 hourly intervals, ie, until day 5. The oral dose was based on surface area with the following schedule: 0.3 to 0.6 m2, 2 mg; 0.6 to 1 m2, 3 mg; and greater than 1 m2, 4 mg. Vomiting on the first day of chemotherapy was reported in group A by one patient and by one patient in group B. Vomiting during days 2 to 5 was reported by two group-A patients and by three group-B patients. Nausea was recorded on day 1 by one patient in group A, and two in group B, and on days 2 to 5 by three patients in group A, and by seven in group B. All patients were alert during treatment with ondansetron and there was no dystonia. There were no changes in renal function or hematology values that could be ascribed to the study drug. Transient elevations in bilirubin and liver enzymes were observed. We conclude that our results indicate that ondansetron is a safe and extremely effective single-agent antiemetic with minimal side effects, when administered both IV and orally.
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PMID:Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia. 214 19


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