Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Domperidone is the prototype of a new chemical class of compounds with potent gastrokinetic properties. The present study reports on the antiemetic activity and safety of domperidone in dogs. The lowest ED50-values protecting from apomorphine (0.31 mg/kg s.c.) induced emesis are 0.003 mg/kg intravenously, 0.007 mg/kg subcutaneously, 0.03 mg/kg orally and 0.10 mg/kg rectally. Emesis induced by i.v. hydergine, s.c. morphine and oral levodopa is also prevented by low doses of intravenous domperidone, whereas oral copper sulphate-induced emesis is not antagonized. The doses of domperidone needed to induce central depressant effects in dogs (inhibition of conditioned reactions) are at least 300 times higher than the antiemetic doses (apomorphine-induced emesis). Domperidone is also devoid of sedative, adrenolytic and cardiovascular side-effects. The LD50-values in dogs are 42.7 mg/kg intravenously, and more than 160 mg/kg subcutaneously and orally.
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PMID:The antiemetic effects of domperidone, a novel potent gastrokinetic. 741 83

The antiemetic effects of orally administered Y-25130, a potent and selective 5-HT3-receptor antagonist, were compared with those of ondansetron, granisetron, metoclopramide and domperidone. Y-25130 (0.1-1.0 mg/kg) dose-dependently prolonged the latency to the first vomiting and decreased the number of vomitings induced by cisplatin in dogs. The antiemetic effect of Y-25130 against cisplatin-induced vomiting was more potent than that of metoclopramide and ondansetron, but it showed little difference from that of granisetron. The emesis induced by the combined treatment of doxorubicin and cyclophosphamide was also inhibited by Y-25130 (0.1-1 mg/kg) in ferrets. The antiemetic effect of Y-25130 was more potent than that of metoclopramide, almost the same as that of granisetron and less potent than that of ondansetron. Because of a notable difference of potency ranking between Y-25130 and ondansetron in these two tests, a third test was performed to evaluate the inhibitory effect of Y-25130 in ferrets on cisplatin-induced emesis in comparison with that of ondansetron. The antiemetic effect of Y-25130 on cisplatin-induced emesis in ferrets was very similar to that of ondansetron. Domperidone did not inhibit these cytotoxic agents-induced emeses. These results suggest that Y-25130 is an orally active antiemetic compound against cisplatin and doxorubicin/cyclophosphamide-induced emeses; and its the antiemetic potency is similar to those of granisetron and ondansetron, but superior to those of metoclopramide and domperidone.
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PMID:The effects of orally administered Y-25130, a selective serotonin3-receptor antagonist, on chemotherapeutic agent-induced emesis. 810 29

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0-3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 +/- 6.4% retention of isotope 2 h after the meal compared with 37.0 +/- 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.
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PMID:Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson's disease. 939 20

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypothesis. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D2 receptor antagonist metoclopramide. This drug also has 5HT3 receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT4 receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.
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PMID:Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies? 987 82

The anti-emetic and pharmacological profile of AS-8112 ((R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridinecarboxamide.2 fumarate), a novel and potent dopamine D2, D3 and 5-hydroxytryptamine-3 (5-HT3) receptors ligand, was investigated in the present study. In guinea-pig isolated colon, AS-8112 produced a rightward shift of the concentration-response curves of 2-methyl-5HT, a 5-HT3 receptor agonist (pA2 value of 7.04). Other 5-HT3 receptor antagonists also produced such a shift in the following antagonistic-potency order: granisetron> ondansetron=AS-8112>>metoclopramide. In mice, AS-8112 (1.0 - 3.0 mg kg(-1) s.c.) potently inhibited hypothermia induced by the dopamine D3 receptor agonist; R(+)-7-OH-DPAT (R(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetraline) (0.3 mg kg(-1) s.c.). Domperidone and haloperidol, which have affinity for dopamine D3 receptor, also inhibited R(+)-7-OH-DPAT-induced hypothermia. In ferrets or dogs, AS-8112 dose-dependently inhibited emesis induced by R(+)-7-OH-DPAT, apomorphine, morphine or cisplatin with ID50 values of 2.22 microg kg(-1) s.c., 10.5 microg kg(-1) s.c., 14.2 microg kg(-1) i.v. and 17.6 microg kg(-1) i.v., respectively. Moreover, oral administration of AS-8112 significantly inhibited emesis induced by these emetogens. AS-8112 (0.3 mg kg(-1) i.v.) significantly inhibited emesis induced by cyclophosphamide and doxorubicin. In conclusion, AS-8112 is a potent dopamine D2, D3 and 5-HT3 receptors antagonist, and a novel anti-emetic agent with a broad-spectrum of anti-emetic activity. These results suggest that this compound is worthy of clinical investigation.
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PMID:The broad-spectrum anti-emetic activity of AS-8112, a novel dopamine D2, D3 and 5-HT3 receptors antagonist. 1135 Aug 61

Nutrition support in gastroparesis begins with encouraging smaller volume, low-fat, low-fiber meals and, if necessary, liquid caloric supplements. There should be a low threshold for placing a jejunal feeding tube either by laparoscopy or mini-laparotomy. Parenteral nutrition should be used only briefly during hospitalization and not encouraged or sustained as an outpatient. Metoclopramide is now the prokinetic of choice for patients who can tolerate this agent; subcutaneous administration is an important method that allows for continued guaranteed absorption. Low-dosage erythromycin also has a prokinetic role alone or in combination with metoclopramide. Domperidone, a centrally acting antiemetic and prokinetic, is only be available to US citizens who can access sources in Canada or Mexico. Antiemetics should be used extensively because nausea is a very severe debilitating symptom, which is under-appreciated and under-treated by physicians. We recommend scopolamine patches to gain maximal absorption, in spite of vomiting and unpredictable oral intakes. The 5-hydroxytryptamine-3 (5-HT3) antagonists ondansetron and granisetron are the most powerful agents. Relief bands using the P6 acupuncture point are useful adjunct. Special vigilance should be paid to situations that can undermine medical therapy or result in breakthrough symptoms, such as hyperglycemic events in patients with diabetes, migraine headaches, cyclic nausea and vomiting, menstrual cycles, rumination syndrome (psychogenic vomiting), and elevated herpes simplex titers. Most excitingly, the era of gastric electrical stimulation has arrived for patients not responding to standard medical therapy. The dramatic improvement in nausea and vomiting, as well as a sustained evidence of improved quality of life, gastric emptying, nutritional status, and decreased hospitalizations by this device are documented by long-term follow-up of more than a year for patients in this country and world-wide.
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PMID:Gastric Dysmotility and Gastroparesis. 1146 76

The action of domperidone (1 mg/kg, i.p.) on spontaneous behaviour and the emesis and behavioural change induced by apomorphine (0.25 mg/kg, s.c.) were studied in the ferret. Domperidone was inactive to modify spontaneous behaviour but apomorphine-induced emesis and increased locomotor activity (distance travelled and velocity of movement; P<0.05); the emesis, but not the modification of locomotor activity was antagonized significantly (P<0.01) by domperidone. However, apomorphine did not modify significantly other behavioural measures (i.e. lip licking, rearing, burrowing, backward walking, curling-up activity, or defecatory frequency; P>0.05). The action of apomorphine to modify behaviour and its interaction with domperidone in this species is discussed in relation to animal models of nausea.
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PMID:Differential action of domperidone to modify emesis and behaviour induced by apomorphine in the ferret. 1596 78

Apomorphine, a non-ergot derivative, is a potent, directly acting dopamine receptor agonist with high affinity to D4, lower to D2, D3, D5, the lowest to D1-like dopamine receptors as well as to serotonin and adrenoreceptors. Subcutaneous apomorphine is currently used in Parkinson's disease as an add-on to levodopa therapy or monotherapy for management of sudden, unexpected and refractory to levodopa-induced off state and fluctuation in advanced stage of illness. Many clinical trials have shown markedly (about 50-72%) reduced time of off phases. Other indications include the challenge test for determining the dopaminergic responsiveness. Apomorphine is used subcutaneously either as intermittent rescue injections or continuous infusions. Several other routes - transdermal, sublingual, intranasal, rectal and intravenous infusion - have been tried. Oral administration is not recommended. Apomorphine has rapid onset of antiparkinsonian action, qualitatively comparable to that of levodopa, short duration of action and stable efficacy with usually mild adverse events similar to other dopamine agonists. Domperidone or trimethobenzamide should be introduced before starting apomorphine treatment to reduce occurrence of peripheral adverse events (nausea, vomiting, orthostatic hypotension). Dyskinesias, sleep disturbances, hallucinations, delusion, oedema and yawning can occur, but some side effects are connected only with a specific route (for example skin nodules appearing during subcutaneous administration). Despite its long history, apomorphine is registered and used in only a few countries. Apomorphine warrants wider application in treatment of advanced Parkinson disease but the high cost of the drug, the necessity of concomitant treatment for prevention of side effects and subcutaneous administration restrict its use.
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PMID:[Apomorphine in off state--clinical experience]. 1794 58

Domperidone is an antiemetic that is often prescribed for children with acute gastroenteritis in Japan. In this study, the authors assessed the efficacy of domperidone prescription in combination with oral rehydration treatment (ORT) in the treatment of vomiting during acute gastroenteritis in children during the early period. They performed a prospective multicenter randomized trial in Japan. Patients received either ORT or ORT and domperidone prescription. The primary outcome was the proportion of patients who had vomiting during the first 2 hours after randomization. A total of 56 children were eligible; 24 received ORT alone, and 32 received ORT and prescribed domperidone suppository. Results showed that 27.3% of children in the ORT group vomited as compared with 20.7% of children in the ORT and domperidone group (P = .41). In this study, it appears that domperidone in combination with ORT in the treatment of acute gastroenteritis does not reduce vomiting in the early period.
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PMID:Domperidone with ORT in the treatment of pediatric acute gastroenteritis in Japan: a multicenter, randomized controlled trial. 2223 29

Domperidone is a prokinetic drug used for diabetic gastro paresis, hiccoughs, and vomiting. It is a peripheral D2 receptor antagonist with selective peripheral activity restricted to the upper gastro intestinal tract. It is not known to cross the blood brain barrier and hence, lacks neurological side effects. We would like to report a case of domperidone induced galactorrhea in a young female who presented with galactorrhea and other symptoms suggestive of prolactinoma.
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PMID:Domperidone induced galactorrhea: an unusual presentation of a common drug. 2383 83


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