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)

The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing postoperative nausea and vomiting in surgical patients was studied. Fifty women were randomized in a double-blind manner to receive either two 8 mg doses of intravenous ondansetron or two doses of placebo vehicle: the first given just before general anesthesia induction and the second 8 hours later. During the first 24 postoperative hours, the number of emetic episodes was recorded and the subjects rated their nausea on a scale from 0 to 10. Ondansetron-treated subjects had fewer emetic episodes (p less than 0.001) and lower subjective nausea scores (p less than 0.001). The number of complete responders (no emetic episodes and no rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more effective than placebo in the prophylaxis of postoperative nausea and vomiting. The adverse event profile for ondansetron was similar to that of placebo.
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PMID:Ondansetron is effective in decreasing postoperative nausea and vomiting. 138 67

Ondansetron is a 5-HT3 receptor antagonist which is effective and well tolerated as an antiemetic for emesis induced by cancer chemotherapy and radiation therapy, and in the prevention and treatment of postoperative nausea and vomiting. Ondansetron is rapidly absorbed after oral administration (tmax 1.9 h) with an absolute bioavailability of around 60%. Its terminal elimination half-life is 3.5 h and it is extensively hepatically metabolized. Plasma clearance is 0.38 litre h-1 kg-1 and volume of distribution is 1.8 litre kg-1. Plasma clearance is reduced by age (31% reduction) and hepatic failure (80% reduction in severe failure). In patients undergoing general anaesthesia there is a slight prolongation of terminal half-life, which is not of clinical significance. Ondansetron is very well tolerated in volunteer studies. Headache, mild abdominal pain, and constipation occur infrequently. There is no evidence for effects of ondansetron on cardiac function (electrocardiogram, cardiac output, blood pressure and heart rate), and haemostatic function in volunteers and patients. Respiratory depression induced during general anaesthesia is not potentiated by ondansetron. No drug interactions have been noted with temazepam, atracurium, alfentanil and alcohol in man. There are also no interactions seen in animal studies using pentobarbitone, morphine, neostigmine, prednisolone and diazepam.
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PMID:Clinical pharmacology of ondansetron in postoperative nausea and vomiting. 142 20

This study was carried out to assess the efficacy of oral ondansetron, a new 5HT3 receptor antagonist, in patients undergoing thyroid surgery. It included 60 patients, randomly assigned to two groups, and receiving orally, 1 h before induction of anaesthesia, either 8 mg of ondansetron (n = 29) or a placebo (n = 30). One patient was excluded. The same anaesthetic protocol, consisting of 3 to 5 micrograms.kg-1 of fentanyl, 4 to 6 mg.kg-1 of thiopentone, and 0.5 mg.kg-1 of atracurium, was used in all. Anaesthesia was maintained with 50% nitrous oxide in oxygen with 0.8 to 1% endtidal concentration of isoflurane and additional boluses of 0.1 mg of fentanyl as required. The incidence and intensity of nausea, graded mild, moderate or severe, and the incidence of vomiting were recorded postoperatively. During the first twelve hours after surgery, 40% of patients in the placebo group had nausea (16.7% mild, 20% moderate and 6.7% severe), and 50% vomited. In the ondansetron group, nausea and vomiting occurred in 13.8% and 20.4% of patients respectively. The 4 patients in the latter group complained of major nausea. The differences between the groups were statistically significant: p = 0.025 for nausea and p = 0.042 for vomiting. It is concluded that oral ondansetron, 8 mg taken orally 1 h before surgery, significantly reduces the incidence of nausea and vomiting during the first twelve postoperative hours. As it is easy to use and has no side-effects, it might be of interest in day-case surgery patients, despite its high cost.
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PMID:[Prevention of postoperative nausea and vomiting by ondansetron]. 147 80

We examined ethanol's interactions with serotonin (5-HT) receptor-mediated [3H]5-HT high-affinity uptake by adult rat forebrain synaptosomes. The serotonergic transport mechanism was chosen because ethanol consumption patterns can be manipulated by serotonin receptors and uptake blockers. We report that a dose of ethanol which causes general anesthesia in humans (54 mM) applied in vitro enhanced rat synaptosomal [3H]5-HT uptake after 5 min at 37 degrees C. Similar levels of stimulation by 54 mM ethanol were seen in hippocampal, cerebral cortex and brainstem synaptosomes. Significant inhibition of uptake was not detected until concentrations of ethanol reached 2.1 M, which is lethal in vivo. Ryanodine and the 5-HT2 agonist, DOI, are believed to cause an increase in intracellular Ca2+ levels. We observed that they also caused an elevation of [3H]5-HT uptake, and this stimulation was less than additive with the ethanol-induced increase. Inhibition of the 5-HT3, receptor-mediated Na+ channel with the antagonist ICS 205930, partially reversed ethanol's stimulatory effects on [3H]5-HT uptake. Blockade of voltage-dependent Na+ flux with tetrodotoxin and lidocaine, however, had no effect on the stimulation by ethanol. But tetraethylammonium, which blocks voltage-dependent K+ channels, partially counteracted ethanol's action on [3H]5-HT uptake. These compounds had no effect on uptake by themselves. These results indicate that ethanol's stimulation of [3H]5-HT uptake involves a rise in [Ca2+]i which is sensitive to voltage-dependent K+ flux and 5-HT3 receptor-mediated Na+ flux, and would decrease the availability of synaptic 5-HT.
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PMID:Ethanol stimulates [3H]5-HT high-affinity uptake by rat forebrain synaptosomes: role of 5-HT receptors and voltage channel blockers. 164 10

Molecular cloning of cDNAs coding for ligand-gated ion channel subunits makes it possible to study the pharmacology of recombinant receptors with defined subunit compositions. Many laboratories have used these techniques recently to study actions of agents that produce general anesthesia. We review the effects of volatile and intravenous anesthetics on recombinant GABAA, glycine, AMPA, kainate, NMDA, and 5HT3 receptors. Evidence for and against specific ligand-gated ion channel subunits as targets responsible for anesthesia or the side effects of anesthetic agents is discussed for each type of receptor. Subunit specific actions of some of the agents suggest that construction and testing of certain chimeric receptor subunits may be useful for defining the amino acid sequences responsible for anesthetic actions.
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PMID:Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition. 758 87

One subunit of the 5-hydroxytryptamine3 (5-HT3) receptor has been cloned, and expression of cDNA coding for this protein in Xenopus oocytes results in the formation of homomeric ion channels. In the present study, this system was used to define the sensitivity of the 5-HT3 receptor to alcohols and anesthetics. Ethanol, in pharmacologically relevant concentrations, potentiated 5-HT-mediated currents, with the greatest potentiation observed at lower concentrations of 5-HT. Likewise, butanol stimulated the receptor but with greater efficacy and potency than ethanol. The volatile anesthetics isoflurane, halothane and 1,2,2-trifluorocyclobutane (F3) all enhanced 5-HT3 receptor function. Concentrations of these anesthetics below the minimal alveolar concentration for anesthesia (MAC) produced significant stimulation of 5-HT-mediated currents. Similar to the alcohols, the greatest enhancement of 5-HT3 receptor function by anesthetics was seen at lower concentrations of 5-HT. However, anesthetics were substantially more efficacious than ethanol in enhancing 5-HT3 receptor function. In the presence of 0.5 microM 5-HT, maximal stimulation by ethanol was approximately 50%, but anesthetic enhancement of 5-HT3 receptor-mediated currents did not reach a maximum. Over the concentrations tested, anesthetics potentiated 0.5 microM 5-HT-mediated currents by approximately 25% to 400%. The intravenous anesthetic propofol did not enhance 5-HT3 receptor function or change the potentiation of this receptor by halothane. These results suggest that alcohols and volatile anesthetics have similar actions on 5-HT3 receptor function, which is in agreement with results of studies with other members of the superfamily of ligandgated ion channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes. 796 11

Ondansetron, a selective 5-HT3 receptor antagonist, has recently been shown, in a dose of 8 mg, to be superior to 1.25 mg droperidol in preventing postoperative vomiting. There are indications that a dose of 4 mg of ondansetron may be just as effective in reducing postoperative nausea and vomiting as a dose of 8 mg. The aim of this study was to evaluate the efficacy and the adverse effects of 4 mg ondansetron in the prevention of postoperative nausea and vomiting compared to droperidol in patients undergoing surgery with inhalation anaesthesia supplemented with alfentanil. METHODS. Following institutional approval, 40 ASA physical status I and II women scheduled for minor gynaecological surgery gave informed consent to participate in this randomized, double-blind comparative study. Five minutes before induction of general anaesthesia, 20 patients received a single intravenous (i.v.) dose of 4 mg of ondansetron and the remaining 20 received 1.25 mg droperidol i.v. Anaesthesia was induced with 2.1-4 mg/kg of thiopental and 0.1 mg of alfentanil i.v. and maintained with 65% nitrous oxide and 1.5%-3% enflurane in oxygen. On pain stimuli another 0.2-0.4 mg of alfentanil was given. Total effective antiemetic response was defined as the absence of nausea and vomiting for 24 h postoperatively. The incidence of nausea, vomiting and the number of patients showing total antiemetic response as well as the incidence of adverse effects were compared with the chi 2 test and P < 0.05 was considered significant. RESULTS. Patients were similar with respect to age, height, body weight and total anaesthetic agents received. Duration of anaesthesia and the time until awakening was not significantly different among groups. Postoperatively 7 out of 20 patients given 4 mg of ondansetron and 3 out of 20 patients with droperidol vomited (n.s.). The incidence of nausea was 11 out of 20 in the ondansetron group, and 4 out of 20 in the droperidol group (P < 0.05). Sixteen patients in the droperidol group and 8 patients in the ondansetron group showed a total effective antiemetic response (P < 0.05). Postoperative sedation and well-being scores did not differ significantly among groups. CONCLUSION. Our results show that for the prevention of postoperative nausea and vomiting 4 mg of Ondansetron was inferior to 1.25 mg of droperidol. The drugs were given intravenously prior to general anaesthesia for minor gynaecological surgery with nitrous oxide and enflurane in oxygen supplemented with small boluses of alfentanil.
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PMID:[Ondansetron as prophylaxis for postoperative nausea and vomiting. A prospective randomized double-blind comparative study with droperidol]. 797 72

Nausea and vomiting are frequent problems in the postoperative period. The introduction of 5-HT3 receptor antagonists has stimulated interest and research in this area. The paper reviews the etiology, physiology, prophylaxis and treatment of postoperative nausea and vomiting. Before using specific antiemetic prophylaxis it is important to evaluate patient risk factors, surgical stimuli and method of anaesthesia. The choice of antiemetic drugs for treatment and prophylaxis should be guided by consideration of effect mechanism, side-effects, clinical documentation and total costs. No single drug is fully effective and combination therapy should be considered in resistant cases.
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PMID:[Postoperative nausea and vomiting]. 807 48

Postoperative nausea and vomiting is a major concern for patients undergoing outpatient surgery under general anaesthesia, and may complicate and delay discharge from hospital. This paper evaluates the safety and efficacy of ondansetron, a 5-HT3 receptor antagonist, in the treatment of postoperative nausea and vomiting. One thousand patients in 30 centres in the United States who received general anaesthesia and developed postoperative nausea and vomiting were studied. In a randomised, double-blind, stratified and parallel designed protocol, patients received either ondansetron 1, 4, 8 mg or placebo for nausea or vomiting occurring within 2 h of entry into the Post Anaesthesia Care Unit. Subsequent episodes of vomiting, nausea scores, laboratory and clinical safety data and adverse events were evaluated during the 24-h study period. In a separate study, pharmacokinetic data were compared for intramuscularly and intravenously administered ondansetron. Each dose of ondansetron was significantly better than placebo in reducing nausea from control values during the initial 2-h study period, and in preventing further emesis over 24 h. There were no significant differences in the incidence of adverse events, changes in laboratory values or measures of vital signs in the ondansetron groups compared to the placebo group. Dose comparisons between the three treatment groups showed that ondansetron 4 mg is the optimal dose to treat postoperative nausea and vomiting. Ondansetron is a well tolerated, efficacious antiemetic which has a similar side effect profile to placebo. Intramuscular administration has the same systemic availability as intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Anaesthesia 1994 Jan
PMID:Single dose intravenous ondansetron for the 24-hour treatment of postoperative nausea and vomiting. 812 59

The potency of Ondansetron (Zofran, Glaxo), a highly specific 5HT3 antagonist in preventing the very unfavorable complication during introducing anesthesia, i.e. a Bezold-Jarisch reflex-like reaction, was studied in a clinical trial. A total of 20 patients (12 males and 8 females aged 19-65 years) admitted for clinical surgical treatment participated in the trial. Zofran (8 mg in 500 ml Ringer solution) was injected intravenously one hour before intubation at a flow rate of 8 ml. min-1. Systolic and diastolic blood pressure, central venous pressure, breathing frequency and minute ventilation, pCO2 and pO2 in venous blood, electrocardiogram monitoring (ECG) and several common features such as spontaneous muscle activity, palpebral reflexes, skin and mucose surfaces were continuously observed. Visual, auscultatory and X-ray control of the lungs was effected. It was found that blockade of 5HT3 receptors prevented the appearance of Bezold-Jarisch reflex-like reaction. The drug could successfully be used in anesthesiological practice.
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PMID:Evaluation of ondansetron as a drug for premedication. 820 75


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