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)

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

Emesis in chemotherapy containing Cisplatinum (DDP) is still a therapeutical dilemma. Emesis and nausea cause the cessation of a potential curative therapy in up to 10% of patients treated with DDP. We studied the antiemetic effectiveness of the selective Serotonin (5HT3)-receptor-antagonist Ondansetron (GR 38032F, Glaxo) in patients receiving high dose platinum chemotherapy. All patients suffered from severe emesis and were refractory to any standard antiemetic regimen (Metoclopramid). We studied the efficacy of the new drug against acute and delayed emesis following platinum chemotherapy. All adverse events are listed. Thirty four courses (n = 17 patients) of a platinum-containing regimen were analyzed so far. A sufficient antiemetic efficacy was observed in 56% of the courses. In 32 of 34 course (94%) the patients preferred the new drug compared with the standard antiemetic regime (Metoclopramid). In most cases only minor adverse events--which do not require any medical therapy--occurred. The most common adverse events were headache, constipation, dry mouth, abdominal discomfort and elevation of liver enzyme level without any clinical symptoms. One patient needed bowel surgery for severe constipation based on widespread intra-abdominal carcinosis.
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PMID:[Refractory vomiting with cisplatin therapy. Prospective study with the serotonin receptor antagonist GR 38032F]. 215 May 51

The results of an open study designed to evaluate the prevention of cisplatin-induced emesis by the specific 5-HT3 receptor antagonist ICS 205-930 are reported. Fifty-four cancer patients, treated with diverse chemotherapy regimens, all including cisplatin (greater than = 50 mg/m2), received ICS 205-930 for a total of 165 courses. ICS 205-930 (10 mg) was given i.v. immediately before the cisplatin infusion and a second 10-mg dose was given immediately after. In 109 courses (66%) the patients did not have any vomiting episodes. Nausea was absent in 44.8% of courses. More than 3 vomiting episodes occurred only in 17 (10.4%) courses, and severe nausea only in 11 (6.6%). ICS 205-930 was extremely well tolerated. Mild headache occurred during 7 courses (4.2%) in 4 patients, hypotension during 5 courses (3%) in 3 patients and lipothymia in 2 courses (1.2%) in 2 patients. These results suggest that ICS 205-930 is an effective and well tolerated antiemetic drug in patients receiving cisplatin chemotherapy.
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PMID:Prevention of nausea and vomiting in cisplatin-treated patients by a selective 5-hydroxytryptamine (5-HT3) receptor antagonist, ICS 205-930. 228 99

GR38032F is a specific 5-HT3 (serotonin) receptor antagonist with antiemetic activity in animal and early human studies. We performed a dose-ranging phase I study of GR38032F in 43 evaluable patients receiving cisplatin 60 120 mg/m2 for the first time (38 of these patients were chemotherapy-naive). Intravenous GR38032F was administered over a dose range from 0.01 to 0.48 mg/kg given three times at four-hour intervals beginning one half hour before cisplatin, and patients were observed for 24 hours. An additional five patients were treated with 0.18 mg/kg given three times at six-hour intervals. Excellent antiemetic efficacy was noted, with 44% of patients experiencing no vomiting and 26% no nausea. Major protection from vomiting (less than or equal to 2 episodes) and from nausea (less than or equal to 2 hours) was experienced by 81% and 44%, respectively. Mild to moderate headache (40%), lightheadedness (21%), and elevated transaminase (19%) were the most common adverse events reported. One patient experienced an apparent hypersensitivity reaction that responded to conventional medications. No extrapyramidal reactions or akathisia were seen. GR38032F was effective through most of the dose range. However, efficacy decreased at the 0.01 mg/kg level and number and intensity of adverse events increased at the 0.48 mg/kg level. Analysis of those patients receiving high-dose cisplatin (100 to 120 mg/m2) revealed a positive association of GR38032F dose and antiemetic activity (Fisher's exact test, two-sided; P less than .05). The 5-HT3 receptor antagonists may provide antiemetic efficacy similar to high-dose metoclopramide without antidopaminergic toxicity. The maximum recommended dose on this schedule of GR38032F is 0.36 mg/kg.
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PMID:Dose ranging phase I study of the serotonin antagonist GR38032F for prevention of cisplatin-induced nausea and vomiting. 252 64

Ondansetron is a 5-HT3 receptor antagonist which has shown activity in the prevention of nausea and vomiting resulting from cytotoxic therapy. This paper describes the results of studies evaluating the efficacy of oral ondansetron in controlling radiation-induced emesis. Initial non-randomised studies showed that doses of 4 mg q.d.s. or 8 mg t.d.s. of ondansetron achieved complete or major control of vomiting in 77-91% of patients and mild or absence of nausea in 72-77% following single exposure high-dose (8-10 Gy) radiotherapy to the upper abdomen. A subsequent double-blind, prospective, randomised trial compared ondansetron 8 mg t.d.s. with metoclopramide 10 mg t.d.s. in the prevention of emesis following single radiation doses of 8-10 Gy to the upper abdomen. On the day of radiotherapy, ondansetron achieved significantly greater control of vomiting and retching (P less than 0.001) and nausea (P = 0.001) than metoclopramide. An advantage for ondansetron was also seen on days 2 and 3 after irradiation, although this did not reach a statistically significant level. Only two patients, out of 154, in all the studies experienced side effects attributable to ondansetron: one developed headache and the other experienced headache and vertigo. These studies show that ondansetron is a safe drug, with activity in the prevention of radiation-induced emesis and significantly greater efficacy than metoclopramide in the control of nausea and vomiting following single exposure upper abdominal high-dose radiotherapy.
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PMID:Clinical studies with ondansetron in the control of radiation-induced emesis. 253 96

In a phase I study of BRL43694A, a 5HT3-receptor antagonist, a single dose of 40 micrograms/kg was given to 24 patients. All patients received cytostatic treatment expected to cause nausea and vomiting. During the first 24 h, 12 patients were completely protected from nausea and vomiting, 4 experienced nausea and 8 had moderate vomiting; mild headache occurred in 10 patients. No cardiovascular (including ECG) changes took place. Apart from headache, no neurological side effects occurred.
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PMID:A phase I study of a new 5HT3-receptor antagonist, BRL43694A, an agent for the prevention of chemotherapy-induced nausea and vomiting. 254 9

The safety and tolerability of dolasetron mesylate, a potent and selective 5-HT3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double-blind, placebo-controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were monitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (ECG) intervals and electroencephalographic (EEG) patterns. Overall, the percentage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8%) or placebo (10/16; 62.5%); most adverse events were mild in severity. Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointestinal (increased appetite and nausea), and visual adverse events and taste alterations. No clinically significant changes in laboratory variables were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) were noted in several subjects at 1 to 2 hours after infusion at doses > or = 3.0 mg/kg. Transient, mild blood pressure decreases were observed in five subjects, including one on placebo. Dolastron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are ongoing for antiemetic indications.
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PMID:A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers. 756 Feb 51

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


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