Original Article
Efficacy of Ondansetron (Gr 38032F) and the Role of Serotonin in Cisplatin-Induced Nausea and Vomiting
N Engl J Med 1990; 322:810-816March 22, 1990
- Abstract
- Abstract
We compared the efficacy and safety of ondansetron (GR 38032F), a selective antagonist of serotonin S3 receptors, with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer. The patients received either three intravenous doses of ondansetron (0.15 mg per kilogram of body weight) or normal saline (placebo) at four-hour intervals, beginning 30 minutes before the administration of cisplatin.
Nausea and vomiting were markedly diminished in the group given ondansetron. The median time to the first episode of emesis was 2.8 hours in the placebo group and 11.6 hours in the ondansetron group (P<0.001 ); the median number of episodes in 24 hours was 5.5 in the placebo group and 1.5 in the ondansetron group (P<0.001); the mean (±SEM) number of regurgitations or dry heaves per episode was 3.2±0.5 in the placebo group and 1.17±0.1 in the ondansetron group (P<0.001). None of the 14 patients given ondansetron, but 12 of 14 given placebo, required treatment with antiemetic-rescue agents for the control of nausea and vomiting. There were no adverse effects attributable to ondansetron.
The urinary excretion of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, was increased in all patients two to six hours after they received cisplatin chemotherapy, and the increases paralleled the episodes of emesis. We conclude that ondansetron is an effective and safe agent for controlling the nausea and vomiting induced by cisplatin treatment. We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells, and that ondansetron acts by blocking S3 receptors for serotonin. (N Engl J Med 1990; 322:810–6.)
Media in This Article
Figure 1
Increased Urinary Excretion of 5-HIAA in Individual Patients with Cancer Who Were Treated with Cisplatin.Figure 2
Episodes of Emesis (○) in Relation to Amounts of Urinary 5-HIAA (●) Excreted after Cisplatin Chemotherapy.Article Activity
- Article
NAUSEA and vomiting are common side effects of antimetabolites and cytotoxic drugs.1 Cisplatin (cis-dichloro-diammineplatinum II), an agent highly effective against a variety of cancers (including testicular, ovarian, urinary-bladder, and head and neck cancers), produces the most severe nausea and emesis of any chemotherapeutic agent.2 3 4 Until recently, the mechanisms by which radiation and chemotherapeutic agents induce nausea and emesis have been unknown.5 6 7 8 Consequently, antiemetic therapy has been empirical, leading to the testing of agents whose mechanisms of action are poorly understood. Antidopaminergic, anticholinergic, and antihistaminic agents, glucocorticoids, benzodiazepines, marijuana, nabilone, and other drugs have been employed either alone or in combination to prevent the nausea and emesis induced by cytotoxic drugs.2 , 4 , 9 10 11 12
Recent investigations performed in laboratory animals have revealed that selective antagonists of serotonin S3 receptors prevent the vomiting induced by cisplatin.13 14 15 16 17 The efficacy and safety of these agents in preventing chemotherapy-induced nausea and emesis in patients with cancer are currently under clinical investigation. Promising results have been obtained in open-label (uncontrolled) clinical trials in human subjects.18 19 20 These observations, as well as others, have led to the proposal that serotonin may be the mediator of the nausea and emesis induced by chemotherapy.6 , 7
In this study we investigated the antiemetic efficacy of ondansetron (GR 38032F; Glaxo), a selective antagonist of S3 serotonin receptors devoid of antidopaminergic properties, in patients receiving cisplatin chemotherapy. The changes in the release and metabolism of serotonin that were induced by cisplatin chemotherapy were evaluated by measuring the urinary excretion rate of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin.
Methods
Study Design
A randomized, double-blind, placebo-controlled, parallel-study design was employed to investigate the efficacy and safety of ondansetron in the control of nausea and emesis induced by chemotherapeutic regimens containing cisplatin. In addition, we investigated whether cisplatin increased the urinary excretion of 5-HIAA.
Patients
Patients with histologically confirmed cancer were eligible for the study if they were 18 years of age or older, had not had previous chemotherapy, and had a Karnofsky performance score of at least 60 percent. They were excluded if they had evidence of uncontrolled cardiovascular or cerebrovascular disease, a serum creatinine concentration above 180 μmol per liter (2 mg per deciliter), a serum alanine aminotransferase concentration more than twice the upper limit of normal, or uncontrolled nausea and vomiting due to other organic causes. No study patient received concurrent radiation therapy or antiemetic medication within the 48 hours before the study or during the 24-hour study period. Written informed consent was obtained from all patients before any study drugs were administered, and the protocol was evaluated and accepted by the institutional review boards of all study centers.
Pretreatment and Follow-up Examinations
The pretreatment evaluation consisted of a complete history and physical examination, a 12-channel electrocardiographic assessment, a complete blood count with differential, and a serum biochemistry profile. Laboratory tests were repeated 24 hours after administration of the study drug. Urine samples for the measurement of 5-HIAA and creatinine were collected at 2-hour intervals, beginning 2 hours before cisplatin therapy was begun (base line) and ending 10 hours later. A 14-hour urine sample was obtained to complete the 24-hour collection.
Chemotherapy
All patients received cisplatin in a dose of at least 50 mg per square meter of body-surface area, dissolved in 500 ml of 5 percent dextrose in 0.45 percent sodium chloride and administered as a 60-minute intravenous infusion. Patients received hydration consisting of 1.5 to 2 liters of 5 percent dextrose in 0.45 percent sodium chloride over the 12-to-18-hour period before cisplatin infusion and received two doses of mannitol (18 g in 100 ml of normal saline) five minutes before and after the infusion. Any other chemotherapeutic agent was administered immediately after the second infusion of mannitol. Hydration with 5 percent dextrose in 0.45 percent sodium chloride was continued at a rate of 150 to 200 ml per hour for the next 12 hours and at 100 ml per hour from 12 to 24 hours after cisplatin infusion.
Antiemetic and Antiemetic-Rescue Treatment
Patients were randomly assigned (on a one-for-one basis) to receive three intravenous doses of either ondansetron or placebo, according to a computer-generated randomization scheme from the Department of Biostatistics at Glaxo. Ondansetron (1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-lH-imidazol-l-yl)methyl] carbazol-4-one, hydrochloride dihydrate; Glaxo) was supplied in a 10-ml vial containing 20 mg of drug. Identical vials containing only normal saline were used as placebo. The dose of ondansetron (0.15 mg per kilogram of body weight) was dissolved in 50 ml of normal saline. The study drug was infused over a period of 15 minutes, beginning 30 minutes before the initiation of cisplatin therapy and four and eight hours after the initial dose.
Antiemetic-rescue treatment was administered if patients experienced three episodes of emesis in one hour, or if the intensity of nausea and emesis required immediate treatment. In these cases, the patients were not withdrawn from the study but were given the following drugs intravenously, in sequence, over a period of 15 minutes: diphenhydramine, 50 mg; dexamethasone, 20 mg; diazepam, 5 mg; and metoclopramide, 2 mg per kilogram. Rescue therapy was repeated if nausea and emesis recurred. The administration of antiemetic-rescue treatment was considered to indicate insufficient efficacy of the antiemetic treatment.
Evaluation of Response
Patients were continuously monitored for nausea and emesis throughout the 24-hour study period by a trained observer who recorded the number, time, and intensity of each episode of emesis. The total number of episodes was calculated by adding the number of episodes of vomiting and the number of episodes of dry retching. The patients assessed the severity of nausea during the 24-hour study period according to a visual-analogue scale (developed at the Sloan—Kettering Institute, New York); the assessment was completed immediately before the first dose of ondansetron or saline and 24 hours after cisplatin infusion. In addition to the episodes of nausea and emesis occurring during the 24-hour inpatient observation period, those occurring over the next 72 hours were recorded by the patients on a diary card. The patients were interviewed at the end of the study in order to assess the information on the card. All adverse events were recorded, and the severity of the event and its relation to the study drug were assessed by the observer.
The frequency of emesis (measured from the time of its onset after initiation of cisplatin infusion, as the number of episodes) was expressed by "emetic score I." This score was the sum of the reciprocals of the time (in hours) elapsed since the beginning of cisplatin infusion at which each episode of emesis occurred (i.e., if episodes occurred after two and four hours, the score would be 0.75[0.5±0.25]). Both the frequency and severity of emesis were expressed by "emetic score II." This weighted score was calculated as score I was, except that each episode was multiplied by the number of vomits occurring during it (i.e., if episodes occurred after two and four hours and four vomits occurred during each episode, the score would be 3[(0.5 × 4) + (0.25 × 4)]).
Urinary Excretion of 5-HIAA
The urinary excretion of 5-HIAA was measured in the patients and in six healthy volunteers (three men and three women 23 to 44 years old and weighing 48 to 75 kg) who received similar hydration. 5-HIAA was quantitated by means of high-performance liquid chromatography with electrochemical detection (Bioanalytical Systems, West Lafayette, Ind.). The detector potential was maintained at 550 mV in relation to the value of a silver—silver chloride reference electrode. Urine samples were diluted 1:50 (vol/vol) with 0.1 M perchloric acid, mixed, and centrifuged, and an aliquot (30 μl) was injected into the Chromatograph. Separation was achieved with a Biophase 5-μm, C18 reversed-phase column (25 cm by 4 mm [internal diameter] ). The mobile phase consisted of 0.1 M citric acid, 0.05 M sodium phosphate, 1 mM disodium EDTA, and 17 percent (vol/vol) methanol (pH 4.5). The retention time for 5-HIAA was 8.04 minutes, and the sensitivity of the method was sufficient to detect 30 pg of 5-HIAA. The urinary concentration of 5-HIAA was corrected for the creatinine concentration. Urinary creatinine was measured with a commercially available colorimetric kit (Direct Creatinine; Bioanalytics Laboratories, Palm City, Fla.).
Statistical Assessment
The chi-square test was used to compare the ondansetron and placebo groups with respect to sex, race or ethnic origin, and alcohol consumption, and the F-test to compare them with respect to age, weight, and height. The Wilcoxon rank-sum test was used to compare the two study treatments with respect to the number and intensity of episodes of emesis and the time to the first episode. Visual-analogue scales were used to measure the severity of nausea, and the Wilcoxon rank-sum test was used for between-treatment comparisons. The chi-square test was used to compare the numbers of patients with adverse events. Fisher's exact test was used to compare clinical laboratory test results obtained before antiemetic treatment with those obtained after treatment. All tests were two-tailed; a P value below 0.05 was considered to indicate statistical significance.
Results
Antiemetic Efficacy of Ondansetron
A total of 28 patients with cancer who were placed on chemotherapeutic regimens containing cisplatin entered and completed the study. Half received ondansetron, and the other half placebo. There were no significant differences between the two groups in age, sex, weight, or alcohol consumption (Table 1Table 1
Characteristics of the Patients and the Chemotherapy Administered.). Nearly 60 percent of patients in each group had genitourinary cancer (neoplasm of the ovary, urinary bladder, or vulva); however, a greater proportion of patients with head and neck cancers were assigned to the placebo group (Table 1). All patients received cisplatin either alone or combined with other anticancer agents. The dose of cisplatin ranged from 50 to 120 mg per square meter; the mean (±SEM) dose was 78.2±6.7 mg per square meter in the ondansetron group and 72.9±6.2 mg per square meter in the placebo group.The measurements of the antiemetic efficacy in the early, intense period of nausea and emesis after cisplatin chemotherapy are summarized in Tables 2Table 2
Characteristics of Cisplatin-lnduced Emesis. and 3Table 3
Assessment by Patients of Control of Nausea and Emesis.. Ondansetron was superior to placebo in all aspects of antiemetic efficacy. Patients who received placebo had intense nausea and emesis within two to four hours after the initiation of cisplatin treatment. No patient who received ondansetron required antiemetic-rescue treatment, whereas 12 of 14 patients who received placebo required this treatment (P<0.001). The number of episodes of emesis was significantly higher in the placebo group than in the ondansetron group (respective medians, 5.5 vs. 1.5; P<0.001). Treatment with ondansetron not only reduced the number of episodes but also markedly delayed the onset of emesis (2.8 hours with placebo vs. 11.6 hours with ondansetron; P<0.001). The assessments made by the patients indicated that ondansetron provided significantly better control of nausea than did placebo (P = 0.034) and better satisfaction with the control of nausea and emesis (P = 0.009; Table 3).The intensity of emesis was evaluated by measuring the number of vomits per episode and the total number of vomits on the first study day. Among the patients who experienced emesis, the mean number of vomits per episode was significantly lower in the ondansetron group than in the placebo group (1 vs. 3.2; P<0.001). The frequency of vomiting (emetic score I) was 8-fold lower with ondansetron than with placebo, and the severity of vomiting (emetic score II) was 20-fold lower with ondansetron (P<0.001).
Data on delayed nausea and emesis were obtained in 13 patients given ondansetron and 11 given placebo (Table 4Table 4
Frequency and Duration of Delayed Emesis.*). Interestingly, in both groups all episodes of emesis reported between 24 and 96 hours after cisplatin therapy were characterized as being very mild, consisting of only one vomit per episode. Eighty-five percent of patients given ondansetron and 55 percent of those given placebo (who had also received antiemetic-rescue treatment) had at least one episode of delayed emesis (P<0.05). A similar number of patients who received either ondansetron or placebo experienced no emesis on the second through the fourth day after cisplatin chemotherapy.There were no differences between the treatment groups in the incidence or severity of adverse events, regardless of whether or not the events were considered by the investigator to be drug related. The incidence of diarrhea was 14 percent in the placebo group and 7 percent in the ondansetron group. Headaches occurred in 15 percent of patients given ondansetron and 21 percent of those given placebo. No extrapyramidal reactions were observed. There were no significant differences between the two groups in the results of hematologic and blood chemistry evaluations.
Role of Serotonin in Cisplatin-lnduced Nausea and Emesis
The urinary concentration of 5-HIAA, the rate of excretion of 5-HIAA, and the ratio of the urinary excretion of 5-HIAA to that of creatinine were determined before, during, and after cisplatin infusion. The excretion rates of 5-HIAA and creatinine and the ratio of these rates were corrected for the changes in urine volume produced by the administration of intravenous fluids and mannitol. All patients had a significant increase in the urinary excretion of 5-HIAA after they received cisplatin (Fig. 1Figure 1
Increased Urinary Excretion of 5-HIAA in Individual Patients with Cancer Who Were Treated with Cisplatin.). The excretion rate of 5-HIAA increased from an average of 490±42 μg per hour in the two hours before cisplatin infusion to 1242±212 μg per hour in the four-to-six-hour period after infusion (P<0.001). When corrected for the creatinine level (nanograms of 5-HIAA per microgram of creatinine), the 5-HIAA:creatinine ratio averaged 7.0±0.8 before cisplatin infusion and increased to 17.±1.6 four to six hours after infusion. Similar increases in the urinary excretion of 5-HIAA above base line were observed in the placebo group (350±39 percent, or 1.8 mg) and the ondansetron group (420±55 percent, or 1.6 mg) (P>0.1). The relation between the occurrence of emesis and the increase in urinary 5-HIAA excretion was evaluated in the patients given placebo (before they received antiemetic-rescue treatment). Interestingly, the onset and development of emesis occurred in parallel with the rise in the urinary excretion of 5-HIAA (Fig. 2Figure 2Episodes of Emesis (○) in Relation to Amounts of Urinary 5-HIAA (●) Excreted after Cisplatin Chemotherapy.). In the healthy volunteers, there were no significant changes in the excretion rate of 5-HIAA or in the 5-HIAA: creatine ratio after the controls were given hydration and mannitol.Discussion
Studies in laboratory animals and open-label clinical trials in patients with cancer have indicated that antagonists of serotonin S3 receptors provide protection against chemotherapy-induced nausea and emesis.18 19 20 21 22 23 24 Although these pilot trials yielded preliminary data on the efficacy and safety of these agents, the interpretation of the results has been limited by the lack of control groups, the heterogeneity of the populations of patients studied, the use of chemotherapy regimens on which there is little information about the natural course of emesis, and the lack of assessment of delayed emesis. The present study was designed to circumvent these limitations.
In this study, we demonstrated that ondansetron is more effective than placebo in preventing cisplatin-induced nausea and emesis. None of the patients given the serotonin antagonist required antiemetic-rescue treatment, whereas 12 of the 14 patients given placebo required such treatment. The intense nausea and emesis occurring two to eight hours after cisplatin infusion were abolished by ondansetron, the onset of the first episode of emesis was delayed, and in addition, any later episode was mild and infrequent. The antiemetic efficacy of ondansetron was either comparable or superior to that reported for high-dose metoclopramide or dexamethasone.3 , 4 , 11 , 25 , 26
This controlled trial employed antiemetic-rescue treatment as an index with which to assess the clinical efficacy of an antiemetic drug; a combination of diphenhydramine, dexamethasone, diazepam, and metoclopramide was selected as rescue therapy and was given when three episodes of emesis developed within an hour.25 , 27 , 28 This combination was quite effective in stopping emesis, and the relief was associated with the induction of sleep.
In previous studies, delayed nausea and emesis occurred in most patients receiving moderate to high doses of cisplatin, despite good initial control with antiemetic regimens containing metoclopramide, dexamethasone, lorazepam, or haloperidol.26 , 29 30 31 32 33 In the present study, the incidence of delayed emesis was higher among the patients given ondansetron than the patients given placebo who received antiemetic-rescue treatment. However, it should be emphasized that in both groups of patients, the delayed emesis was very mild. No patient had more than a single vomit per episode. In addition, the episodes were not spontaneous, as observed during the initial period of emesis, but were most often triggered by manipulating the oral cavity (brushing teeth and using mouthwash) and, in the morning, by standing up after getting out of bed. Similar observations have been made by Sridhar and Donnelly.28 Since ondansetron has a half-life of 3 to 6 hours, it is possible that its antiemetic effect became negligible in the ondansetron group as early as 9 hours after the last dose (17 hours after cisplatin infusion began), whereas it was extended in the placebo group because of the administration of dexamethasone and diazepam. Another possibility is that the mechanism responsible for delayed emesis is different from that responsible for the initial period of intense emesis after cisplatin infusion.
There were no side effects that could be attributed to ondansetron. The drug did not produce sedation, sleepiness, diarrhea, or extrapyramidal symptoms or signs. It may thus be especially useful in adults less than 30 years old, among whom extrapyramidal side effects are reported to occur in more than 25 percent who receive high-dose metoclopramide.34
Serotonin appears to be the mediator of chemotherapy-induced nausea and emesis (Fig. 3Figure 3
Model Explaining the Role of Serotonin in Chemotherapy-Induced Nausea and Emesis.). In the present study we demonstrated that ondansetron, a selective antagonist of serotonin S3 receptors, inhibits the intense nausea and emesis induced by cisplatin chemotherapy. The antiemetic efficacy of metoclopramide may also be due to its ability to block serotonin S3 receptors.6 The following observations support the hypothesis of mediation by serotonin (Fig. 3): in ferrets, pretreatment with para-chlorophenylalanine, an inhibitor of serotonin synthesis, prevented cisplatin-induced emesis35; and in humans, the urinary excretion of –HIAA increased in parallel with the development of nausea and emesis after cisplatin infusion (present study).Serotonin S3 receptors (also known as M receptors) have been demonstrated in sympathetic and parasympathetic postganglionic neurons and fibers, in sensory neurons in the enteric nervous system, and in the central nervous system.36 37 38 39 40 In peripheral nerve fibers, the activation of S3 receptors by serotonin induces depolarization and increases nervous activity, an effect blocked by S3-receptor antagonists.37 , 38 , 41 More than 80 percent of the total body serotonin is present in the gastrointestinal tract,42 located in the enterochromaffin cells of the mucosal layer, with only small amounts in submucosa, the muscularis, and the myenteric plexus.43 44 45 46 47 It has been estimated that the human gastrointestinal tract contains 4 to 8 mg of serotonin; its half-life ranges from 7 to 12 hours.48 , 49 Available evidence indicates that urinary 5-HIAA is derived mainly from serotonin in the gastrointestinal tract.42 , 50 51 52
On the basis of these findings, the large increase in the urinary excretion of 5-HIAA (1.4 to 1.9 mg in six hours) observed after cisplatin infusion should represent the amount of serotonin released from enterochromaffin cells. This is supported by the observation that platelet serotonin content was not affected two to eight hours after cisplatin administration (Cubeddu LX: unpublished observations). The released serotonin could stimulate afferent fibers and initiate sensory signals to the chemoreceptor trigger zone, the vomiting center, or both, inducing nausea and emesis. The sensory signals appear to travel through the vagus and greater splanchnic nerve, since studies in ferrets have shown that denervation of abdominal viscera by bilateral abdominal vagotomy and section of the greater splanchnic nerve abolished cisplatin-induced emesis16 (Fig. 3). This working model would explain the initial period of intense nausea and emesis following cisplatin chemotherapy and the very high antiemetic efficacy of ondansetron. High concentrations of serotonin S3 receptors have been demonstrated in the area postrema—nucleus tractus solitarii region of the medulla.38 These findings suggest that ondansetron may have a central site of action as well.
Supported by a grant from Glaxo Inc. to Grupo de Investigaciones ClinicoTerapéuticas Florida.
We are indebted to Mr. Juan Malave for valuable technical assistance, to Drs. C. de Johgn, U. Dos Ramos, H.-J. Goldsztajn, Z. Pastran, G. Rojas-Martinez, and G. Velazquez for their cooperation in recruiting patients, to N. Barrios, I. Dominguez, S. Lara, R. Aponte, and L. Urbaneja for nursing assistance, and to Alison Richard for help in preparing the manuscript.
Source Information
From the Division of Clinical Pharmacology, Department of Pharmacology, University of North Carolina at Chapel Hill (L.X.C.); the Department of Pharmacology, Central University of Venezuela (I.S.H.), and Perez Carreno Hospital of Caracas (N.T.F.), Caracas, Venezuela; and Glaxo Inc., Research Triangle Park, N.C. (A.L.F.) Address reprint requests to Dr. Cubeddu at the Department of Pharmacology, Central University of Venezuela, Apartado Nueva Granada, Caracas, Venezuela.
- References
References
1
Laszlo
Full Text | Web of Science | Medline2
Laszlo
CrossRef | Web of Science | Medline3
Gralla
Full Text | Web of Science | Medline4
Gralla
CrossRef | Web of Science | Medline5
Borison
CrossRef | Web of Science | Medline6
Fozard
CrossRef | Web of Science7
Andrews
CrossRef | Web of Science | Medline8
Carl
CrossRef | Web of Science9
Vincent
CrossRef | Web of Science | Medline10
Wampler
CrossRef | Web of Science | Medline11
Aapro
Web of Science | Medline12
Gagen
Web of Science | Medline13
Costall
CrossRef | Web of Science | Medline14
Costall 15
Brittain 16
Hawthorn
Web of Science | Medline17
Miner
Web of Science | Medline18
Leibundgut
CrossRef | Web of Science | Medline19
Green
Web of Science20
Stables 21
Hesketh
Web of Science | Medline22
Kris
Web of Science | Medline23
Kris
CrossRef | Web of Science | Medline24
Plezia 25
Kris
CrossRef | Web of Science | Medline26
Loeffler 27
Plezia
Medline28
Sridhar
CrossRef | Web of Science | Medline29
Von Hoff
Medline30
Kris
Web of Science | Medline31
Passalacqua 32
Louvet 33
Bernard 34
Kris
Web of Science | Medline35
Barnes 36
Gaddum
Web of Science | Medline37
Richardson 38
Kilpatrick
CrossRef | Web of Science | Medline39
Richardson
CrossRef | Web of Science | Medline40
Costall
CrossRef | Web of Science | Medline41
Suprenant
CrossRef | Web of Science | Medline42
Bertaccini 43
Feldberg 44
Resnick
Web of Science | Medline45
Erspamer 46
Gershon
Web of Science | Medline47
Robinson
Web of Science | Medline48
Udenfriend
Web of Science | Medline49
Erspamer
CrossRef | Web of Science | Medline50
Bertaccini
CrossRef | Web of Science51
Rosenberg 52
Bertaccini
CrossRef | Web of Science
- Citing Articles (128)
Citing Articles
1
Peter Greaves. 2012. Nervous System and Special Sense Organs. , 799-866.
CrossRef2
David P King, Sara Paciga, Eve Pickering, Neal L Benowitz, Laura J Bierut, David V Conti, Jaakko Kaprio, Caryn Lerman, Peter W Park. (2011) Smoking Cessation Pharmacogenetics: Analysis of Varenicline and Bupropion in Placebo-Controlled Clinical Trials. Neuropsychopharmacology
CrossRef3
Qian Wan, Zhibin Liu, Wenzhen Peng, Jianmei Wang, Xufeng Li, Yi Yang. (2011) BnRCH gene inhibits cell growth of Hela cells through increasing the G2 phase of cell cycle. Human Cell
CrossRef4
Katherine E Fero, Leena Jalota, Cyrill Hornuss, Christian C Apfel. (2011) Pharmacologic management of postoperative nausea and vomiting. Expert Opinion on Pharmacotherapy 12:15, 2283-2296
CrossRef5
Felipe Melo Cruz, Daniel Iracema Gomes Cubero, Patrícia Taranto, Tatiana Lerner, Andrea Thaumaturgo Lera, Michele Costa Miranda, Mariana Cunha Vieira, Ângelo Bezerra Souza Fêde, Fernanda Schindler, Mércia Maleckas Carrasco, Samuel Oliveira Afonseca, Hélio Pinczowski, Auro Giglio. (2011) Gabapentin for the prevention of chemotherapy- induced nausea and vomiting: a pilot study. Supportive Care in Cancer
CrossRef6
N. Percie du Sert, J. A. Rudd, C. C. Apfel, P. L. R. Andrews. (2011) Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists. Cancer Chemotherapy and Pharmacology 67:3, 667-686
CrossRef7
BU. K. Li, Bhanu K. Sunku. 2011. Vomiting and Nausea. , 88-105.
CrossRef8
So Young Um, Song Wha Chae, Hyun Joo Park, Myeon Woo Chung, Sun Ok Choi, Hwa Jeong Lee. (2010) Simple determination of azasetron in rat plasma by column-switching high-performance liquid chromatography. Journal of Separation Science 33:23-24, 3638-3643
CrossRef9
Atto Billio, Enrico Morello, Mike J Clarke, Atto Billio. 2010. Serotonin receptor antagonists for highly emetogenic chemotherapy in adults. .
CrossRef10
Hideaki Ayuhara, Risa Takayanagi, Kiyoshi Okuyama, Koichi Yoshimoto, Takeshi Ozeki, Haruko Yokoyama, Yasuhiko Yamada. (2009) Receptor occupancy theory-based analysis of interindividual differences in antiemetic effects of 5-HT3 receptor antagonists. International Journal of Clinical Oncology 14:6, 518-524
CrossRef11
Qiu-hai Qian, Wang Yue, Yao-xia Wang, Zhi-hong Yang, Zhan-tao Liu, Wen-hui Chen. (2009) Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks. Archives of Pharmacal Research 32:4, 565-573
CrossRef12
Albert Tuca, Rosa Roca, Carme Sala, Josep Porta, Gala Serrano, Jesús González-Barboteo, Xavier Gómez-Batiste. (2009) Efficacy of Granisetron in the Antiemetic Control of Nonsurgical Intestinal Obstruction in Advanced Cancer: A Phase II Clinical Trial. Journal of Pain and Symptom Management 37:2, 259-270
CrossRef13
D. T. Beattie, J. A. M. Smith. (2008) Serotonin pharmacology in the gastrointestinal tract: a review. Naunyn-Schmiedeberg's Archives of Pharmacology 377:3, 181-203
CrossRef14
Vincent Launay-Vacher, Jean-Baptiste Rey, Corinne Isnard-Bagnis, Gilbert Deray, Mikael Daouphars. (2008) Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemotherapy and Pharmacology 61:6, 903-909
CrossRef15
Qing-Hui YUAN, Li-Xin ZHOU. (2007) A Density Functional Study on the Hydrolysis Process of Non-classical Transplatin(II) with Two Same Planar Heterocycle Amines. Chinese Journal of Chemistry 25:11, 1604-1611
CrossRef16
Guillaume Savoye, Maud Brung-Lefebvre, Mickael Bouin, Céline Maillot, Philippe Denis, Philippe Ducrotté. (2007) Effects of Ondansetron on Gastric Tone and Motility Changes Induced by a Prolonged Intraduodenal Infusion of Nutrients. Results of a Placebo-Controlled Study. Digestive Diseases and Sciences 52:10, 2676-2683
CrossRef17
Atto Billio, Mike J Clarke, Enrico Morello, Atto Billio. 2006. Comparison of clinical efficacy of serotonin receptor antagonists in highly emetogenic chemotherapy. .
CrossRef18
Edith P. Mitchell. (2006) Gastrointestinal Toxicity of Chemotherapeutic Agents. Seminars in Oncology 33:1, 106-120
CrossRef19
M. Raquel Brown, Kenita S. Rogers. 2006. Supportive Medical Care and Pain Management in Feline Cancer Patients. , 665-672.
CrossRef20
M. IKEDA, M. YASUI, H. FUKUNAGA, I. SESHIMO, O. TAKAYAMA, M. IKENAGA, H. YAMAMOTO, M. OHUE, M. SEKIMOTO, M. MONDEN. (2005) Clinical usefulness of oral granisetron hydrochloride for alleviation of delayed nausea and vomiting induced by CPT-11. European Journal of Cancer Care 14:5, 435-439
CrossRef21
T. Fujita, S. Yokota, M. Sawada, M. Majima, Y. Ohtani, Y. Kumagai. (2005) Effect of MKC-733, a 5-HT3 receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study. Journal of Clinical Pharmacy and Therapeutics 30:6, 611-622
CrossRef22
E. Oddby-Muhrbeck, S. Eksborg, A. Helander, P. Bjellerup, S. Lindahl, P. Lonnqvist. (2005) Blood-borne factors possibly associated with post-operative nausea and vomiting: an explorative study in women after breast cancer surgery. Acta Anaesthesiologica Scandinavica 49:9, 1346-1354
CrossRef23
Ronald de Wit, Matti Aapro, Peter R Blower. (2005) Is there a pharmacological basis for differences in 5-HT3-receptor antagonist efficacy in refractory patients?. Cancer Chemotherapy and Pharmacology 56:3, 231-238
CrossRef24
P. Axelsson, S. E. Thorn, M. Wattwil. (2004) Betamethasone does not prevent nausea and vomiting induced by ipecacuanha. Acta Anaesthesiologica Scandinavica 48:10, 1283-1286
CrossRef25
Fazlul Huq, Hassan Daghriri, Jun Qing Yu, Philip Beale, Keith Fisher. (2004) Studies on the synthesis and characterization of four trans-planaramineplatinum(II) complexes of the form trans-PtL(NH3)CL2 where L = 2-hydroxypyridine, 3-hydroxypyridine, imidazole, and imidazo(1,2-α)pyridine. European Journal of Medicinal Chemistry 39:8, 691-697
CrossRef26
Masaru Minami, Toru Endo, Masahiko Hirafuji, Naoya Hamaue, Yanxia Liu, Tsutomu Hiroshige, Masahiro Nemoto, Hideya Saito, Mitsuhiro Yoshioka. (2003) Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity. Pharmacology & Therapeutics 99:2, 149-165
CrossRef27
Jean Lachaine, Ralph Crott. (2003) Cost-effectiveness of antiemetics use during cancer chemotherapy. Expert Review of Pharmacoeconomics & Outcomes Research 3:3, 263-272
CrossRef28
D. Newby, S. Hill. (2003) Use of pharmacoeconomics in prescribing research. Part 2: cost-minimization analysis - when are two therapies equal?. Journal of Clinical Pharmacy and Therapeutics 28:2, 145-150
CrossRef29
Møller, Jacob E., Connolly, Heidi M., Rubin, Joseph, Seward, James B., Modesto, Karen, Pellikka, Patricia A., . (2003) Factors Associated with Progression of Carcinoid Heart Disease. New England Journal of Medicine 348:11, 1005-1015
Full Text30
Sachiko Tanihata, Satoko Oda, Sachiko Kakuta, Toshimitsu Uchiyama. (2003) Antiemetic effect of a tachykinin NK1 receptor antagonist GR205171 on cisplatin-induced early and delayed emesis in the pigeon. European Journal of Pharmacology 461:2-3, 197-206
CrossRef31
Lixing Lao, Grant Zhang, Richard H Wong, Aaron K Carter, Richard L Wynn, Brian M Berman. (2003) The effect of electroacupuncture as an adjunct on cyclophosphamide-induced emesis in ferrets. Pharmacology Biochemistry and Behavior 74:3, 691-699
CrossRef32
E. A. Mayer, S. Berman, S. W. G. Derbyshire, B. Suyenobu, L. Chang, L. Fitzgerald, M. Mandelkern, L. Hamm, B. Vogt, B. D. Naliboff. (2002) The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Alimentary Pharmacology and Therapeutics 16:7, 1357-1366
CrossRef33
Pierre C. Nicole, Claude A. Trepanier, Martin R. Lessard. (2002) Nausea and vomiting after laparoscopic surgery are not associated with an increased peripheral release of serotonin. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 49:5, 453-457
CrossRef34
P. Netzer, C. Gaia, S. T. Lourens, P. Reber, S. Wildi, U. Noelpp, E. P. Ritter, H. Ledermann, D. Luscher, L. Varga, J. A. Kinser, M. W. Buchler, U. Scheurer. (2002) Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?. Alimentary Pharmacology and Therapeutics 16:1, 119-127
CrossRef35
Robert I. Parker, Devina Prakash, Rosemary A. Mahan, Debra M. Giugliano, Mark P. Atlas. (2001) Randomized, Double-Blind, Crossover, Placebo-Controlled Trial of Intravenous Ondansetron for the Prevention of Intrathecal Chemotherapy-Induced Vomiting in Children. Journal of Pediatric Hematology/Oncology 23:9, 578-581
CrossRef36
Frank P Bymaster, Julie F Falcone, Delbert Bauzon, John S Kennedy, Kathryn Schenck, Neil W DeLapp, Marlene L Cohen. (2001) Potent antagonism of 5-HT3 and 5-HT6 receptors by olanzapine. European Journal of Pharmacology 430:2-3, 341-349
CrossRef37
Emanuel, Ezekiel J., Miller, Franklin G., . (2001) The Ethics of Placebo-Controlled Trials — A Middle Ground. New England Journal of Medicine 345:12, 915-919
Full Text38
T. Endo, M. Minami, M. Hirafuji, T. Ogawa, K. Akita, M. Nemoto, H. Saito, M. Yoshioka, S.H. Parvez. (2000) Neurochemistry and neuropharmacology of emesis — the role of serotonin. Toxicology 153:1-3, 189-201
CrossRef39
Doe-Young Kim, Michael Camilleri. (2000) Serotonin: a mediator of the brain-gut connection. The American Journal of Gastroenterology 95:10, 2698-2709
CrossRef40
Y Yamada. (2000) Abdominal vagi mediate c-Fos expression induced by X-ray irradiation in the nucleus tractus solitarii of the rat. Autonomic Neuroscience 83:1-2, 29-36
CrossRef41
Sachiko Tanihata, Hiroaki Igarashi, Masami Suzuki, Toshimitsu Uchiyama. (2000) Cisplatin-induced early and delayed emesis in the pigeon. British Journal of Pharmacology 130:1, 132-138
CrossRef42
John A Rudd, John Y.H Tse, Man K Wai. (2000) Cisplatin-induced emesis in the cat: effect of granisetron and dexamethasone. European Journal of Pharmacology 391:1-2, 145-150
CrossRef43
Shigemasa Tomioka, Tomiko Kurio, Kazumi Takaishi, Nobuyoshi Nakajo. (1999) Propofol Is Effective in Chemotherapy-Induced Nausea and Vomiting: A Case Report with Quantitative Analysis. Anesthesia & Analgesia 89:3, 798
CrossRef44
Imtiaz Malik, Imran Moid, Zubair Khan, Masood Hussain. (1999) Prospective Randomized Comparison of Tropisetron With and Without Dexamethasone Against High-Dose Metoclopramide in Prophylaxis of Acute and Delayed Cisplatin-Induced Nausea and Vomiting. American Journal of Clinical Oncology 22:2, 126-130
CrossRef45
D. Petrone, M. Kamin, W. Olson. (1999) Slowing the titration rate of tramadol HCl reduces the incidence of discontinuation due to nausea and/or vomiting: a double-blind randomized trial. Journal of Clinical Pharmacy and Therapeutics 24:2, 115-123
CrossRef46
Claudio Sandoval, Dominic Corbi, Barbara Strobino, M. Fevzi Ozkaynak, Oya Tugal, Somasundaram Jayabose. (1999) Randomized Double-Blind Comparison of Single High-Dose Ondansetron and Multiple Standard-Dose Ondansetron in Chemotherapy-Naive Pediatric Oncology Patients. Cancer Investigation 17:5, 309-313
CrossRef47
Martha E Leatherman, Joseph M Bebchuk, R.David Ekstrom, Amy Durr Heine, Stanley W Carson, Robert N Golden. (1999) The effects of serotonin3 receptor blockade on the psychobiological response to intravenous clomipramine in healthy human subjects. Biological Psychiatry 45:2, 238-240
CrossRef48
Alain Borgeat, Patrick Hasler, Marc Fahti. (1998) Gynecologic Laparoscopic Surgery Is Not Associated with an Increase of Serotonin Metabolites Excretion. Anesthesia & Analgesia 87:5, 1104-1108
CrossRef49
Fuad Lechin, Bertha van der Dijs, Beatriz Orozco, Hector Jara, Isais Rada, Marcel E. Lechin, Alex E. Lechin. (1998) Neuropharmacologic treatment of bronchial asthma with the antidepressant tianeptine: A double-blind, crossover placebo-controlled study*. Clinical Pharmacology & Therapeutics 64:2, 223-232
CrossRef50
Andreas Broocks, Teresa A Pigott, James L Hill, Stephanie Canter, Tana A Grady, Francine L'Heureux, Dennis L Murphy. (1998) Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive–compulsive disorder (OCD): behavioral and biological results. Psychiatry Research 79:1, 11-20
CrossRef51
Camilleri, Ford. (1998) Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders. Alimentary Pharmacology and Therapeutics 12:4, 287-302
CrossRef52
B. Hammas, A. Hvarfner, S.-E. Thörn, M. Wattwil. (1998) Effects of propofol on ipecacuanha-induced nausea and vomiting. Acta Anaesthesiologica Scandinavica 42:4, 447-451
CrossRef53
A JACOT, B BISSONNETTE, J FAVRE, P RAVUSSIN. (1998) Effet de l'ondansétron sur la pression intracrânienne et la pression de perfusion cérébrale chez le patient neurochirurgical. Annales Françaises d’Anesthésie et de Réanimation 17:3, 220-226
CrossRef54
Andreas Bois. (1998) Management der Chemotherapie-induzierten Emesis: Was ist Standard nach 20 Jahren klinischer Forschung?. Medizinische Klinik 93:S1, 3-17
CrossRef55
Trevor W. Hambley. (1997) The influence of structure on the activity and toxicity of Pt anti-cancer drugs. Coordination Chemistry Reviews 166, 181-223
CrossRef56
Enrico Polati, Giuseppe Verlato, Gabriele Finco, Walter Mosaner, Salvatore Grosso, Leonardo Gottin, Anna M. Pinaroli, Stefano Ischia. (1997) Ondansetron Versus Metoclopramide in the Treatment of Postoperative Nausea and Vomiting. Anesthesia & Analgesia 85:2, 395-399
CrossRef57
Norman A. Desbiens, Nancy Mueller-Rizner, Alfred F. Connors, Neil S. Wenger. (1997) The relationship of nausea and dyspnea to pain in seriously ill patients. Pain 71:2, 149-156
CrossRef58
Alain Borgeat, Marc Fathi, Antonella Valiton. (1997) Hyperemesis gravidarum: Is serotonin implicated?. American Journal of Obstetrics and Gynecology 176:2, 476-477
CrossRef59
I Jantunen. (1997) An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting. European Journal of Cancer 33:1, 66-74
CrossRef60
Thomas M. Beck, Martin York, Alex Chang, Rudolph Navari, Walter H. Harvey, Michael Meshad, Daniel Griffin, Alison Wentz. (1997) Oral Ondansetron 8 mg Twice Daily is as Effective as 8 mg Three Times Daily in the Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Cancer Chemotherapy. Cancer Investigation 15:4, 297-303
CrossRef61
Mark G. Kris, Luigi X. Cubeddu, Richard J. Gralla, Didier Cupissol, Leslie B. Tyson, Ennpadam Venkatraman, Howard D. Homesley. (1996) Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin. Cancer 78:10, 2193-2198
CrossRef62
Dyabra Kasabdji, Vedapuri Shanmugam, Appu Rathinavelu. (1996) Effect of cisplatin on dopamine release from PC12 cells. Life Sciences 59:21, 1793-1801
CrossRef63
Andreas Bois, Werner Vach, Rolf Holy, Hanna Kriesinger-Schröder. (1996) 5-Hydroxyindoleacetic acid excretion following combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil plus ondansetron compared to ondansetron alone. Supportive Care in Cancer 4:5, 384-389
CrossRef64
P Brock. (1996) An increased loading dose of ondansetron: a North European, double-blind randomised study in children, comparing 5 mg/m2 with 10 mg/m2. European Journal of Cancer 32:10, 1744-1748
CrossRef65
P. R. F. Davies, P. Warwick, M. O'Connor. (1996) Antiemetic efficacy of ondansetron with patient-controlled analgesia. Anaesthesia 51:9, 880-882
CrossRef66
Tana A. Grady, Andreas Broocks, Stephanie K. Canter, Teresa A. Pigott, Billinda Dubbert, James L. Hill, Dennis L. Murphy. (1996) Biological and behavioral responses to d-amphetamine, alone and in combination with the serotonin3 receptor antagonist ondansetron, in healthy volunteers. Psychiatry Research 64:1, 1-10
CrossRef67
Epstein, Franklin H., , Goyal, Raj K., Hirano, Ikuo, . (1996) The Enteric Nervous System. New England Journal of Medicine 334:17, 1106-1115
Full Text68
Heidi Eriksson, Kari Korttila. (1996) Recovery Profile After Desflurane With or Without Ondansetron Compared With Propofol in Patients Undergoing Outpatient Gynecological Laparoscopy. Anesthesia & Analgesia 82:3, 533-538
CrossRef69
T. ALI-MELKKILÄ, J. KANTO, R. KATEVUO. (1996) Tropisetron and metoclopramide in the prevention of postoperative nausea and vomiting.. Anaesthesia 51:3, 232-235
CrossRef70
Giovanni Mantovani, Antonio Macciò, Alessandro Bianchi, Luigi Curreli, Massimo Ghiani, Ernesto Proto, Maria C. Santona. (1996) Comparison of granisetron, ondansetron, and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial. Cancer 77:5, 941-948
CrossRef71
A MARTONI, B ANGELELLI, M GUARALDI, E STROCCHI, F PANNUTI. (1996) An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens
. European Journal of Cancer 32:1, 82-85
CrossRef72
J.A. Rudd, K.T. Bunce, R.J. Naylor. (1996) The interaction of dexamethasone with ondansetron on drug-induced emesis in the ferret. Neuropharmacology 35:1, 91-97
CrossRef73
Alberto M. Ravelli. (1995) Gastrointestinal function in chronic renal failure. Pediatric Nephrology 9:6, 756-762
CrossRef74
A. Bois, H. G. Meerpohl, H. Kriesinger-Schroeder. (1995) The role of serotonin as a mediator of emesis induced by different stimuli. Supportive Care in Cancer 3:5, 285-290
CrossRef75
Isabelle A. Saphr-Schopfer, Jerrold Lerman, Nancy Sikich, Jonathan Palmer, Ursula Jorch. (1995) Pharmacokinetics of intravenous ondansetron in healthy children undergoing ear, nose, and throat surgery*. Clinical Pharmacology & Therapeutics 58:3, 316-321
CrossRef76
Gary R. Morrow, Jane T. Hickok, Susan N. Rosenthal. (1995) Progress in reducing nausea and emesis. Comparisons of ondansetron (zofran), granisetron (kytril), and tropisetron (navoban). Cancer 76:3, 343-357
CrossRef77
C. W. Ogle, S. -C. G. Hui. (1995) The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats. Experientia 51:8, 786-789
CrossRef78
Jaime Zighelboim, Nicholas J. Talley, Sidney F. Phillips, William S. Harmsen, Alan R. Zinsmeister. (1995) Visceral perception in irritable bowel syndrome. Digestive Diseases and Sciences 40:4, 819-827
CrossRef79
James S. Wohl, Susan M. Cotter. (1995) Approach To Complications Of Anti-Cancer Therapy In Emergency Practice. Journal of Veterinary Emergency and Critical Care 5:1, 61-76
CrossRef80
Jørn Herrstedt. (1995) Development of Antiemetic Therapy in Cancer Patients. Acta Oncologica 34:5, 637-640
CrossRef81
Volker Diehl, Michel Marty. (1994) Efficacy and safety of antiemetics. Cancer Treatment Reviews 20:4, 379-392
CrossRef82
A. L. Billett, S. E. Sallan. (1994) Antiemetics in children receiving cancer chemotherapy. Supportive Care in Cancer 2:5, 279-285
CrossRef83
Rothman, Kenneth J., , Michels, Karin B., . (1994) The Continuing Unethical Use of Placebo Controls. New England Journal of Medicine 331:6, 394-398
Full Text84
Haig P. Bozigian, J. Frederick Pritchard, Ann E. Gooding, Gary E. Pakes. (1994) Ondansetron absorption in adults: Effect of dosage form, food, and antacids. Journal of Pharmaceutical Sciences 83:7, 1011-1013
CrossRef85
MARC R. PERRY, JOHN RHEE, WILLIAM L. SMITH. (1994) Plasma Levels of Peptide YY Correlate with Cisplatin-induced Emesis in Dogs. Journal of Pharmacy and Pharmacology 46:7, 553-557
CrossRef86
NICOLA STONER. (1994) Antiemetics in cancer chemotherapy. International Journal of Pharmacy Practice 2:4, 191-192
CrossRef87
Nicolas Tsavaris, Nicolas Mylonakis, Charalambos Bacoyiannis, Michalis Katsikas, Athina Lioni, Paris Kosmidis. (1994) Comparison of ondansentron versus ondansentron plus methylprednisolone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Journal of Pain and Symptom Management 9:4, 254-258
CrossRef88
C. Schaake-Koning, W. van den Bogaert, O. Dalesio, J. Festen, J. Hoogenhout, P. van Houtte, A. Kirkpatrick, M. Koolen, B. Maat, A. Nijs, A. Renaud, P. Rodrigus, L. Schuster-Uitterhoeve, J. Sculier, N. van Zandwijk, H. Bartelink. (1994) Radiosensitization by cytotoxic drugs. The EORTC experience by the Radiotherapy and Lung Cancer Cooperative Groups. Lung Cancer 10, S263-S270
CrossRef89
Stephen A. Wring, Regina M. Rooney, Colin P. Goddard, Ian Waterhouse, William N. Jenner. (1994) A sensitive radioimmunoassay, combined with solid-phase extraction, for the sub-nanogram per ml determination of ondansetron in human plasma. Journal of Pharmaceutical and Biomedical Analysis 12:3, 361-371
CrossRef90
M. H. PEARMAN. (1994) Single dose intravenous ondansetron in the prevention of postoperative nausea and vomiting. Anaesthesia 49:s1, 11-15
CrossRef91
Andreas du Bois, Werner Vach, Christoph Thomssen, Ulrich Karck, Helmut Madjar, Heiner Prömpeler, Hans G. Meerpohl. (1994) Comparison of the Emetogenic Potential Between Cisplatin and Carboplatin in Combination with Alkylating Agents. Acta Oncologica 33:5, 531-535
CrossRef92
N.W. Read, K.-A. Gwee. (1994) The importance of 5-hydroxytryptamine receptors in the gut. Pharmacology & Therapeutics 62:1-2, 159-173
CrossRef93
S Lecomte, A Adenis, J Bonneterre. (1994) Traitement antiémétique et chimiothérapie : revue générale. La Revue de Médecine Interne 15:11, 752-769
CrossRef94
R. J. NAYLOR, F. C. INALL. (1994) The physiology and pharmacology of postoperative nausea and vomiting. Anaesthesia 49:s1, 2-5
CrossRef95
Wood, Alastair J.J., , Grunberg, Steven M.Hesketh, Paul J.. (1993) Control of Chemotherapy-Induced Emesis. New England Journal of Medicine 329:24, 1790-1796
Full Text96
John H. Gilmore, Robert G. Ruegg, R. David Ekstrom, Bettina Knight, Stanley W. Carson, George A. Mason, Robert N. Golden. (1993) Altered prolactin response to clomipramine rechallenge in healthy subjects. Biological Psychiatry 34:12, 885-888
CrossRef97
J. SIDEROV, J. ZALCBERG, B. CHAMBERS, G. FABINYI. (1993) Migraine following the use of a 5-hydroxytryptamine antagonist. Australian and New Zealand Journal of Medicine 23:5, 527-528
CrossRef98
Oliver H. G. Wilder-Smith, Alain Borgeat, Pierre Chappuis, Marc Fathi, Michel Forni. (1993) Urinary serotonin metabolite excretion during cisplatin chemotherapy. Cancer 72:7, 2239-2241
CrossRef99
Rudolph M. Navari, Wanda S. Province, George M. Perrine, James R. Kilgore. (1993) Comparison of intermittent ondansetron versus continuous infusion metoclopramide used with standard combination antiemetics in control of acute nausea induced by cisplatin chemotherapy. Cancer 72:2, 583-586
CrossRef100
Takeshi Kamato, Hiroyuki Ito, Yukinori Nagakura, Akito Nishida, Hidenobu Yuki, Mayumi Yamano, Keiji Miyata. (1993) Mechanisms of cisplatin- and m-chlorophenylbiguinide-induced emesis in ferrets. European Journal of Pharmacology 238:2-3, 369-376
CrossRef101
I. Angel, H. Schoemaker, M. Prouteau, M. Garreau, S.Z. Langer. (1993) Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties. European Journal of Pharmacology 232:2-3, 139-145
CrossRef102
Ismo T. Jantunen, Martti K. Flander, Mirja I. Heikkinen, Tapio A. Kuoppala, Lase Teerenhovi, Vesa V. Kataja. (1993) Comparison of Ondansetron with Customary Treatment in the Prophylaxis of Nausea and Emesis Induced by Non-Cisplatin Containing Chemotherapy. Acta Oncologica 32:4, 413-415
CrossRef103
George W. Sledge, Lawrence Einhorn, Catherine Nag, Karen House. (1992) Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy. Cancer 70:10, 2524-2528
CrossRef104
Paolo Preziosi, Massimo D'Amato, Renata Del Carmine, Maria Martire, Giacomo Pozzoli, Pierluigi Navarra. (1992) The effects of 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon. European Journal of Pharmacology 221:2-3, 343-350
CrossRef105
Sewa S. Legha, Cynthia Hodges, Sigrid Ring. (1992) Efficacy of ondansetron against nausea and vomiting caused by dacarbazine-containing chemotherapy. Cancer 70:7, 2018-2020
CrossRef106
Naoyuki Yoshida, Hiroko Omoya, Shiro Kato, Tsugutaka Ito. (1992) 5-HT3 receptor antagonist effects of DAT-582, (R) enantiomer of AS-5370. European Journal of Pharmacology 216:3, 435-440
CrossRef107
Berend Olivier, Jan Mos, Jan Van Der Heyden, Guus Van Der Poel, Martin Tulp, Jef Slangen, Rian De Jonge. (1992) Preclinical evidence for the anxiolytic activity of 5-HT3 receptor antagonists: A review. Stress Medicine 8:2, 117-136
CrossRef108
Schaake-Koning, Caro, van den Bogaert, Walter, Dalesio, Otilia, Festen, Jan, Hoogenhout, Jaap, van Houtte, Paul, Kirkpatrick, Anne, Koolen, Mia, Maat, Ben, Nijs, Arie, Renaud, Alain, Rodrigus, Patrick, Schuster-Uitterhoeve, Lon, Sculier, Jean-Paul, van Zandwijk, Nico, Bartelink, Harry, . (1992) Effects of Concomitant Cisplatin and Radiotherapy on Inoperable Non-Small-Cell Lung Cancer. New England Journal of Medicine 326:8, 524-530
Full Text109
David Tattersall, Nigel Newberry, Margaret S. Beer, Mike Rigby, Michael Gilbert, Janet J. Maguire, Nikki Mudunkotuwa, Mark Duchnowski, Alexander T. McKnight, Christopher J. Swain, Clare Kneen, Colin T. Dourish. (1992) L-683,877: Pharmacological profile of a novel 5-HT3 receptor antagonist. Drug Development Research 25:1, 17-28
CrossRef110
Ismo T. Jantunen, Vesa V. Kataja, Risto T. Johansson. (1992) Ondansetron and Tropisetron with Dexamethasone in the Prophylaxis of Acute Vomiting Induced by Non-cisplatin-Containing Chemotherapy. Acta Oncologica 31:5, 573-575
CrossRef111
Russell J. Schilder, Robert F. Ozols. (1992) New Therapies for Ovarian Cancer. Cancer Investigation 10:4, 307-315
CrossRef112
Stéphane Milano, Christian Simon, Laurent Grélot. (1991) In vitro release and tissue levels of ileal serotonin after cisplatin-induced emesis in the cat. Clinical Autonomic Research 1:4, 275-280
CrossRef113
Suzanne M. Evans, Alphonse Galdes, Martin Gall. (1991) Molecular modeling of 5-HT3 receptor ligands. Pharmacology Biochemistry and Behavior 40:4, 1033-1040
CrossRef114
(1991) Precipitation of Ondansetron in Alkaline Solutions. New England Journal of Medicine 325:18, 1315-1316
Full Text115
Marco Turconi, Arturo Donetti, Antonio Schiavone, Angelo Sagrada, Ernesto Montagna, Massimo Nicola, Raffaele Cesana, Carlo Rizzi, Rosella Micheletti. (1991) Pharmacological properties of a novel class of 5-HT3 receptor antagonists. European Journal of Pharmacology 203:2, 203-211
CrossRef116
C. A. Fontes Ribeiro. (1991) Pharmacology of serotonin neuronal systems. Human Psychopharmacology: Clinical and Experimental 6:S1, S37-S51
CrossRef117
Lothar Weissbach, Peter Kirkbride, JohnW Dundee, ChristineM Mcmillan, Fausto Roila, Maurizio Tonato, Albano Del Favero. (1991) Ondansetron. The Lancet 338:8769, 753-754
CrossRef118
A.L. Jones, A.S. Hill, D. Cunningham, M. Soukop, A.W. Hutcheon, J. Cassidy, S.B. Kaye, K. Sikora, D.N. Carney. (1991) Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy. The Lancet 338:8765, 483-487
CrossRef119
D.B. Smith, E.S. Newlands, G.J.S. Rustin, R.H.J. Begent, K.D. Bagshawe, N. Howells, B. McQuade. (1991) Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. The Lancet 338:8765, 487-490
CrossRef120
C. Seynaeve, P.H.M. de Mulder, E. Lane-Allman, P.A. van Liessum, J. Verweij. (1991) The 5-HT3 receptor antagonist ondansetron re-establishes control in refractory emesis induced by non-cisplatin chemotherapy. Clinical Oncology 3:4, 199-203
CrossRef121
Stephen M. Sagar. (1991) The current role of anti-emetic drugs in oncology: a recent revolution in patient symptom control. Cancer Treatment Reviews 18:2, 95-135
CrossRef122
S.M. Sagar, M.A. Bayliss, S.-L. Chong, S. Retsas. (1991) Ondansetron; further progress in the prevention of nausea and vomiting induced by anti-cancer chemotherapy. Clinical Oncology 3:3, 183
CrossRef123
C. Seynaeve, P. H. M. Mulder, J. Verweij. (1991) Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear. Pharmaceutisch Weekblad Scientific Edition 13:1, 1-6
CrossRef124
Keith Bunce, Michael Tyers, Paul Beranek. (1991) Clinical evaluation of 5-HT3 receptor antagonists as anti-emetics. Trends in Pharmacological Sciences 12, 46-48
CrossRef125
(1990) Ondansetron and Cisplatin-Induced Nausea and Vomiting. New England Journal of Medicine 323:21, 1485-1486
Full Text126
Janine M. Barnes, N.M. Barnes, S. Champaneria, Brenda Costall, R.J. Naylor. (1990) Characterisation and autoradiographic localisation of 5-HT3 receptor recognition sites identified with [3H]-(S)-zacopride in the forebrain of the rat. Neuropharmacology 29:11, 1037-1045
CrossRef127
Ali Khojasteh, George Sartiano, Efstathios Tapazoglou, Eric Lester, David Gandara, Stephen Bernard, Andrew Finn. (1990) Ondansetron for the prevention of emesis induced by high-dose cisplatin. A multi-center dose-response study. Cancer 66:6, 1101-1105
CrossRef128
Grunberg, Steven M., . (1990) Making Chemotherapy Easier. New England Journal of Medicine 322:12, 846-848
Full Text
- Letters
