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PubMed2001

Conditioned food aversion in Suncus murinus (house musk shrew) - a new model for the study of nausea in a species with an emetic reflex.

The lack of a small animal model with an emetic reflex in which the relationship between conditioned food aversion and emesis could be investigated prompted a study of the insectivore, Suncus murinus (the house musk shrew). A novel food (either tuna or chicken cat food) was paired (C+) with a single exposure to either nicotine (4 mg/kg sc), motion (1 Hz, 4 cm, 10 min) or lithium chloride (100 mg/kg ip) or was paired (C-) with either saline or sham exposure to motion. Nicotine and motion both induced emesis (retching/vomiting) but lithium chloride did not. All three treatments produced a conditioned food aversion after a single pairing with consumption of C+ food. When given a choice between the two foods, S. murinus given lithium chloride, motion exposure and nicotine consumed, respectively, only 25%, 23% and 1% of their total intake from the C+ food. This study shows that a conditioned food aversion can be readily induced in S. murinus and that the induction of emesis can be uncoupled from food aversion. S. murinus provides a promising new model in which the relationship between emesis, nausea and conditioned food aversion can be investigated.

Animals↗
PubMed2003

Enhanced schistosomicidal efficacy of tartar emetic encapsulated in pegylated liposomes.

The aim of the present study was to evaluate the ability of liposomes to improve the efficacy of tartar emetic (TA) against established Schistosoma mansoni infection. TA was used as a schistosomicidal drug model and both conventional liposomes (CL) and long-circulating pegylated liposomes (LCL) were evaluated. In the first experiment, TA, either free or encapsulated within CL or LCL, was given intraperitoneally (i.p.) as a single dose of 11 mg Sb/kg to mice experimentally infected with S. mansoni. Only the group treated with LCL showed a significant (55%) reduction in the worm burden, compared to the control groups (untreated or treated with empty LCL). In the second experiment, the efficacy of TA-containing LCL was evaluated at a higher dose (27 mg Sb/kg) by both subcutaneous (s.c.) and i.p. routes. Reduction levels of 67 and 82% were achieved by s.c. and i.p. routes, respectively. Strikingly, all mice survived to this high dose of antimony. This is in contrast with free TA that was lethal in 100% of mice at the same dose. The present work demonstrates that LCL reduce the acute toxicity of TA and effectively deliver this drug to S. mansoni during the late stages of parasite infection.

Animals↗
PubMed2003

Reduction of emetic symptoms during cesarean delivery with antiemetics: propofol at subhypnotic dose versus traditional antiemetics.

STUDY OBJECTIVE: To evaluate the efficacy and safety of propofol (at a subhypnotic dose), droperidol, and metoclopramide in reducing emetic symptoms during cesarean delivery. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: University hospital. PATIENTS: 100 ASA physical status I and II parturients undergoing cesarean delivery with spinal anesthesia. INTERVENTIONS: Patients received placebo (saline) followed by placebo (Intralipid(R)), placebo (saline) followed by propofol at a subhypnotic dose (1.0 mg/kg/hr), droperidol 1.25 mg followed by placebo (Intralipid(R)), or metoclopramide 10 mg followed by placebo (Intralipid(R)) intravenously (IV) immediately after clamping of the umbilical cord. MEASUREMENT AND MAIN RESULTS: The percentage of patients who were emesis-free, which was defined as experiencing no nausea, retching, or vomiting, in the intraoperative, postdelivery period was 80% with propofol, 80% with droperidol, and 78% with metoclopramide (p < 0.05), compared with placebo (40%). Severity of nausea was less inpatients who received propofol than in those who received placebo (p < 0.05), and there were no differences seen among the droperidol, metoclopramide, and placebo groups. No clinically serious adverse events as a result of the study drugs were observed in any of the groups. CONCLUSIONS: Prophylactic antiemetic efficacy of propofol at a subhypnotic dose (1.0 mg/kg/hr), droperidol 1.25 mg, and metoclopramide 10 mg is comparable in parturients undergoing cesarean delivery. Moreover, propofol at a subhypnotic dose is effective in the prevention of severe nausea.

Adult↗
PubMed2000

High incorporation of L-amino acids to cereulide, an emetic toxin from Bacillus cereus.

Cereulide is a principal toxin causing emetic syndrome produced by Bacillus cereus. This paper deals with biosynthetic studies on this unusual cyclic depsipeptide toxin from 13C labeled L-amino acid precursors (Val, Leu, Ala) upon cultivation in synthetic media. The analyses were made at atomic level of the constituent amino- or oxy-acids through NMR and ESI-MS/MS spectroscopic methods on cereulide and its hydrolysate dipeptides. The incorporation of the 13C atom was 95% in each O-Val, O-Leu and L-Val, while 40% in D-Ala of cereulide.

Amino Acids↗
PubMed2003

Synthesis and structure-activity relationships of 2-substituted-8-hydroxyadenine derivatives as orally available interferon inducers without emetic side effects.

Recently we reported the adenine derivatives (2-4) as new interferon (IFN) inducers. In the present study, we conducted a detailed structure and activity relationship study of 4 and its related derivatives on IFN inducing activity. From this study, we found that compound 4 exhibited the most potent IFN inducing activity in vitro with a minimum effective concentration of 0.01 microM, and 4 also showed strong IFN-inducing activity at doses of more than 0.3mg/kg by oral administration in mice. This potency was 10-fold stronger than that of Imiquimod. Moreover, 4 did not cause emesis in ferrets even at doses as high as 10mg/kg, whereas, 80% of animals were emetic when orally administered with the same dose of Imiquimod. These results indicate that compound 4 is superior to Imiquimod with respect to efficacy and safety.

Adenine↗
PubMed2004

Use of anti-emetic herbs in pregnancy: women's choices, and the question of safety and efficacy.

The majority of North American pregnant women experience some degree of nausea and vomiting, usually in the first few months of pregnancy. Women utilize many coping strategies, including self-treatment with herbal medicine and other alternative therapies. In a qualitative study of self-care in pregnancy, birth and lactation within a non-random sample of 27 women in British Columbia, Canada, 20 women (74%) experienced pregnancy-induced nausea. Ten of these women used anti-emetic herbal remedies, which included ginger, peppermint, and Cannabis. The safety and efficacy of each of these herbal remedies is discussed here. Only ginger has been subjected to clinical trials among pregnant women, though all three herbs were clinically effective against nausea and vomiting in other contexts, such as chemotherapy-induced nausea and post-operative nausea. While safety concerns exist in the literature for all three herbs with regards to their use by pregnant women, clinical evidence of harm is lacking.

Antiemetics↗
PubMed1999

Two novel anti-emetic principles of Alpinia katsumadai.

Two novel diarylheptanoids named katsumadain A (1) and katsumadain B (2) were isolated from the seeds of Alpinia katsumadai, and their structures were determined by spectroscopic analysis. Both katsumadains A (1) and B (2) showed anti-emetic activities on copper sulfate-induced emesis in young chicks.

Animals↗
PubMed1992

Comparison of the anti-emetic efficacy of different doses of ondansetron, given as either a continuous infusion or a single intravenous dose, in acute cisplatin-induced emesis. A multicentre, double-blind, randomised, parallel group study. Ondansetron Study Group.

A total of 535 chemotherapy naive, hospitalised patients (263 male/272 female) scheduled to receive cisplatin (50-120 mg m-2)-containing regimens participated in a randomised, double-blind, parallel group study to evaluate the efficacy and safety of three intravenous dose schedules of ondansetron in the prophylaxis of acute nausea and emesis. One hundred and eighty two patients received a loading dose of 8 mg of ondansetron followed by a 24 h infusion of 1 mg h-1 (group 1); 180 and 173 patients received single doses of 32 mg (group II) and 8 mg (group III) respectively, followed by a 24 h placebo infusion. Complete and major control (less than or equal to 2 emetic episodes) of acute emesis was achieved in 74% of patients in group I, 78% in group II and 74% in group III. Seventy seven per cent of the patients in group I, and 75% of patients in groups II and III respectively experienced no or mild nausea during the 24 h observation period. A retrospective stratification of the efficacy data on the basis of patient gender showed the response rate in females to be significant lower (43% vs 67%; less than 0.001). Ondanestron was well tolerated; mild headache was the most commonly reported adverse event (11% of patients) with a similar incidence in the three groups of patients. In conclusion, a single intravenous dose of 8 mg of ondansetron given prior to chemotherapy is as effective as a 32 mg daily dose given as either a single dose of a continuous infusion in the prophylaxis of acute cisplatin-induced emesis.

Adult↗
PubMed1999

Safety and efficacy of a continuous infusion, patient controlled anti-emetic pump to facilitate outpatient administration of high-dose chemotherapy.

We evaluated the combination of diphenhydramine, lorazepam, and dexamethasone delivered as a continuous i.v. infusion via an ambulatory infusion pump with patient-activated intermittent dosing (BAD pump) for prevention of acute and delayed nausea/vomiting in patients receiving high-dose chemotherapy (HDC) for peripheral blood progenitor cell (PBPC) mobilization (MOB) or prior to autologous PBPC rescue. The BAD pump was titrated to patient response and tolerance, and continued until the patient could tolerate oral anti-emetics. Forty-four patients utilized the BAD pump during 66 chemotherapy courses, 34 (52%) for MOB and 32 (48%) for HDC with autologous PBPC rescue. The median number of days on the BAD pump during MOB and HDC was 3 (1-6) and 9 (2-19) days, respectively. Complete overall or complete emesis control occurred on 94% of MOB and 89% of HDC treatment days during chemotherapy administration and 72% and 43%, respectively, following chemotherapy administration. Eighty-three percent of MOB and 55% of HDC treatment days were associated with no nausea. While on the BAD pump, no patient experienced severe toxicity or required hospitalization for management of nausea/vomiting. The BAD pump was safe and effective in minimizing nausea and vomiting associated with HDC, and thus, eliminated the need for hospitalization for management of chemotherapy-induced nausea and vomiting.

Adult↗
PubMed1998

Prophylactic anti-emetic therapy with granisetron, droperidol and metoclopramide in female patients undergoing middle ear surgery.

The efficacy of granisetron, droperidol and metoclopramide for the prevention of postoperative nausea and vomiting in female patients undergoing middle ear surgery was compared. In a randomised, double-blind study, 180 patients received granisetron 40 micrograms.kg-1, droperidol 20 micrograms.kg-1 or metoclopramide 0.2 mg.kg-1 given intravenously immediately before induction of anaesthesia (n = 60 for each). A standardised general anaesthetic technique was employed throughout. A complete response, defined as no postoperative nausea and vomiting and no need for another rescue anti-emetic, during the first 3 h after anaesthesia was achieved in 83%, 58% and 55% of patients who had received granisetron, droperidol and metoclopramide, respectively. The corresponding incidence during the next 21 h after anaesthesia was 85%, 54% and 47% (p < 0.05). No clinically important adverse effects were observed in any of the groups. We conclude that prophylactic therapy with granisetron is superior to droperidol or metoclopramide in the prevention of postoperative nausea and vomiting after middle ear surgery.

Adult↗
PubMed1999

Prophylactic anti-emetic efficacy of ondansetron in laparoscopic cholecystectomy under total intravenous anaesthesia. A randomised, double-blind comparison with droperidol, metoclopramide and placebo.

The prophylactic anti-emetic efficacy and safety of pre-operative intravenous ondansetron was evaluated in a randomised, double-blind, comparison with droperidol, metoclopramide and placebo in 160 ASA grade 1 and 2 patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia. The patients were randomly allocated to receive ondansetron (4 mg), droperidol (1.25 mg), metoclopramide (10 mg) or placebo given as a single intravenous dose immediately before induction of a standardised general anaesthetic. There were no significant differences between the four study groups with regard to the demographic and anaesthetic data, postoperative analgesia, postoperative sedation scores, duration of postoperative hospital stay and incidence of adverse events. The incidence of nausea and vomiting was significantly lower (p < 0.05) between 1 h and 4 h after surgery in the ondansetron group compared with the droperidol, metoclopramide and placebo groups. The incidence of nausea was similar in the four groups in the other study periods: 0-1 h and 4-24 h. The incidence of vomiting was lower in the ondansetron, droperidol and metoclopramide groups than in the placebo group between 1 and 4 h but was the same between 4 and 24 h. As a result of the lower incidence of nausea and vomiting between 1 h and 4 h in the ondansetron group, the overall incidence of nausea and vomiting was lower during the first 24 h after surgery in this group than in the other three groups.

Adult↗
PubMed1999

Double-blind comparative study of droperidol, granisetron and granisetron plus dexamethasone as prophylactic anti-emetic therapy in patients undergoing abdominal, gynaecological, breast or otolaryngological surgery.

In this double-blind study the clinical efficacy of a single pre-operative intravenous dose of droperidol 1.25 mg (137 patients), granisetron 1 mg (130 patients) and granisetron 1 mg plus dexamethasone 5 mg (130 patients) was investigated for the prevention of postoperative nausea and vomiting after gynaecological surgery, breast surgery, abdominal surgery and ear, nose and throat surgery. The incidence of nausea in the first 24 h postoperatively was 52% in the droperidol group, 48% in the granisetron group and 34% with the combination, respectively. Both granisetron and granisetron/dexamethasone performed better than droperidol in their effects on vomiting or combined nausea and vomiting (incidence in the first 24 h 22%, 18% and 42%, respectively). The number of emetic episodes during the 5-day study period was significantly higher in the droperidol group (198) than in the granisetron (73) or combination group (78).

Adult↗
PubMed1999

Anti-emetic efficacy of prophylactic granisetron compared with perphenazine for the prevention of post-operative vomiting in children.

We have compared the efficacy of granisetron with perphenazine in the prevention of vomiting after tonsillectomy with or without adenoidectomy in children. In a prospective, randomized, double-blind study, 90 paediatric patients, ASA I, aged 4-10 years, received granisetron 40 mg kg-1 or perphenazine 70 mg kg-1 (n = 45 each) intravenously immediately after an inhalation induction of anaesthesia. A standard general anaesthetic technique was employed throughout. A complete response, defined as no emesis with no need for another rescue antiemetic, during the first 3 h (0-3 h) after anesthesia was 87% with granisetron and 78% with perphenazine (P = 0.204). The corresponding incidence during the next 21 h (3-24 h) after anaesthesia was 87% and 62% (P = 0.007). No clinically serious adverse events were observed in any of the groups. We conclude that granisetron is a better anti-emetic than perphenazine for the long-term prevention of post-operative vomiting in children undergoing general anaesthesia for tonsillectomy.

Adenoidectomy↗
PubMed1999

Ionophoretic properties and mitochondrial effects of cereulide: the emetic toxin of B. cereus.

The emetic toxin of Bacillus cereus, found to cause immobilization of spermatozoa and swelling of their mitochondria, was purified and its structure found to be identical to the earlier known toxin cereulide. It increased the conductance in black-lipid membranes in KCl solutions in an ionophore-like manner. It formed adducts with K+, Na+, and NH4+ but the conductance was highly selective for K+ in relation to Na+ and H+ (three orders of magnitude). The increase in the kinetics of conductance indicated a stoichiometric ratio between the cereulide and K+. Its ionophoretic properties are thus similar to those of valinomycin. In addition, its effects on rat liver mitochondria were similar: it stimulated swelling and respiration in respiring mitochondria in the presence but not in the absence of K+, it reduced the transmembrane potential under these conditions. In nonrespiring mitochondria, swelling was seen in KNO3- but not in NaNO3-containing media, less in acetate. In NaNO3 media addition of the cereulide caused a transient diffusion potential which was reduced by adding K+. It is concluded that the toxic effects of cereulide are due to it being a K+ ionophore.

Animals↗
PubMed1999

Effects of anti-emetic drug (tropisetron) on quality of life during chemotherapy: use of a diary-type questionnaire and application of summary measures for assessment in a randomized, multicentre study. Joint Research Group for Tropisetron Double-Blind Comparative Study.

The role of tropisetron as an anti-emetic drug in the prevention of delayed nausea and vomiting remains unclear. Therefore, effectiveness of tropisetron in patients receiving cancer chemotherapy was evaluated by application of summary measures using a quality of life (QOL) questionnaire. The diary-type QOL self-rating questionnaire was constituted by seven scales. A double-blind randomized, multicentre study was performed in 33 hospitals. Quality of life was measured in 98 patients. Patients receiving cisplatin were randomized to group T (administration of tropisetron before and 4 days after cisplatin treatment) and group P (administration of tropisetron before cisplatin treatment and followed by placebo for 4 days). The rate of complete protection from delayed emesis in the groups T and P was 46.3 and 36.5%. All scales, except social wellbeing changed immediately in both groups and reached a nadir on days 2-3, after that returning to the control levels during 2 weeks after cisplatin treatment. Group T was significantly better than group P in physical wellbeing, mental wellbeing, functional wellbeing and global QOL scores summarized by area under the curve and Difmax (maximum differences of QOL scales' score from the best score throughout the entire period). These results indicate that continuous administration of tropisetron could contribute to preventing patient QOL influenced by cisplatin treatment, and the combined use of summary measures may be useful for the evaluation of QOL in cancer clinical trial.

Adult↗
PubMed2003

Case-control study of teratogenic potential of thiethylperazine, an anti-emetic drug.

OBJECTIVE: Thiethylperazine is a commonly used anti-emetic drug during pregnancy in Hungary. One experimental study in mice and rats found an increased occurrence of cleft palate after the use of thiethylperazine during pregnancy but the human data of thiethylperazine have not been reported. Thus, the aim of the study was to investigate the possible human teratogenic effect of thiethylperazine. DESIGN: Case-control approach. SETTING: The teratogenic potential of thiethylperazine was evaluated in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. SAMPLE: Of 38,151 newborn infants without any congenital abnormalities (control group), 746 (2.0%) had mothers who were treated with thiethylperazine, while of 22,843 cases with congenital abnormalities, 411 (1.8%) had mothers who were treated with thiethylperazine during pregnancy. METHODS: Case-control pair analysis. MAIN OUTCOME MEASURES: Different congenital abnormalities. RESULTS: The pairs of cases with congenital abnormalities and their matched controls without congenital abnormalities were compared and this approach showed a somewhat higher rate of cleft lip +/- palate (OR: 2.0 with 95% CI: 1.0-4.0) in infants born to mothers with thiethylperazine treatment during the first trimester of pregnancy. CONCLUSION: Our data do not indicate clear teratogenic effect of thiethylperazine, however, a weak association was found between thiethylperazine use and cleft lip +/- palate.

Abnormalities, Drug-Induced↗
PubMed2003

Pharmacological profile of AS-9705, a novel benzotriazolecarboxamide derivative, as a gastroprokinetic agent with potent anti-emetic activity.

The pharmacological profile of AS-9705 ((R)-N-(1-ethyl-1H-hexahydroazepin-3- yl)-6- methoxy-1H-benzotriazole-5-carboxamide fumarate monohydrate, CAS 219622-61-4), a novel gastroprokinetic agent with potent anti-emetic activity, was investigated in the present study. AS-9705 inhibited [3H]spiperone binding to human dopamine D2.long receptors, and [3H]R(+)-7-OH-DPAT binding to human dopamine D3 receptors (IC50 values of 58.5 +/- 14.0 and 60.8 +/- 7.8 (nmol/l), respectively) and had negligible affinity (IC50 > 10 mumol/l) for other neurotransmitter recognition sites examined. Moreover, in ferrets or dogs, AS-9705 dose-dependently inhibited emesis induced by R(+)-7-OH-DPAT and apomorphine with ID50 values of 0.05 mg/kg p.o. and 0.04 mg/kg p.o., respectively. AS-9705 dose-dependently enhanced normal gastric emptying and potently inhibited the delay in gastric empting induced by apomorphine, morphine, cisplatin, clonidine and cholecystokinin in rats. Furthermore, in conscious fasting dogs, AS-9705 dose-dependently stimulated gastric motility. In conclusion, AS-9705 is a novel gastroprokinetic agent with potent antiemetic activity and minimal CNS adverse effects and is, therefore, worthy of clinical investigation.

Animals↗
PubMed1976

In vitro studies on the use of penicillamine with tartar emetic against Schistosoma mansoni worms.

In vitro studies were carried out to test Sb125 tartar emetic (T.E.) in concentrations of 75, 100, 125, 150 and 200 mug/ml of rabbit serum and these concentrations together with penicillamine in ratios ranging from 1:1 to 1:6 for their effect on the motility and antimony uptake by Schistosoma mansoni worms. The motility was observed microscopically every half hour for six hours and the Sb125 content was measured by a scintillation counter at one hour intervals for five hours. Results indicate that the ratio in which penicillamine is used with T.E. is very important. The antimony uptake by the worm is reduced, and the onset of T.E. action is delayed when it is used with penicillamine in a ratio exceeding 1:2.

Animals↗