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)

Metoclopramide, 4-amino-5-chloro-2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders. Published data have indicated that metoclopramide assists radiological identification of lesions in the small intestine, facilitates duodenal intubation and small intestine biopsy, and eases emergency endoscopy in upper gastro-intestinal haemorrhage. Metoclopramide reduces post-operative vomiting and radiation sickness, and ameliorates some types of drug-induced vomiting. It may provide symptomatic relief in dyspepsia and possibly in vertigo, reflux oesophagitis and hiccups, but further controlled trials are needed to confirm the efficacy of metoclopramide in these proposed areas of use. It promotes gastric emptying prior to anaesthesia. Its effects in healing gastric ulcer and preventing relapse of duodenal ulcer remain unproven. Side-effects are few and transient, though alarming extrapyramidal reactions can occur in a small proportion of patients receiving therapeutic doses but more usually following excessive doses in young subjects. They respond rapidly to withdrawal of the drug.
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PMID:Metoclopramide: a review of its pharmacological properties and clinical use. 78 7

This randomised, single-blind, parallel-group study was carried out in 48 French pneumology centres to compare the anti-emetic efficacy of ondansetron and an alizapride plus methylprednisolone (ALI/MPS) combination in patients receiving high-dose cisplatin. A total of 220 patients were recruited of whom 209 were evaluable (100 on ondansetron and 109 on ALI/MPS). Thirty minutes before cisplatin, patients received either ondansetron (8 mg i.v.) or alizapride (4 mg/kg i.v.) combined with methylprednisolone (500 mg i.v.). The ondansetron and alizapride injections were repeated 4 and 8 h later. Thereafter, patients received oral ondansetron (8 mg) or alizapride (50 mg) 3 times daily for 5 days. Ondansetron was significantly superior to ALI/MPS in the control of acute emesis (p less than 0.001); 88/100 (88%) of ondansetron, and 69/109 (63%) of ALI/MPS patients experienced less than 3 emetic episodes. Similarly, ondansetron was superior to ALI/MPS for the control of acute nausea (visual analogue scale at 24 h; 13 vs. 22 mm respectively, p = 0.0012). The superiority of ondansetron over days 2-6 was not as great as that over the first 24 h, although there was a trend in favour of ondansetron. More patients treated with ondansetron wished to take the same anti-emetic treatment again (83% for ondansetron vs. 56% for ALI/MPS, p less than 0.001). Both treatments were well tolerated. This study shows that ondansetron is superior to a benzamide-corticosteroid combination in the control of acute cisplatin-induced emesis.
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PMID:A comparison of ondansetron with alizapride plus methylprednisolone in the control of cisplatin-induced emesis. The French Pneumology Group for the Ondansetron Study. 138 30

5-HT3 receptor antagonists, ondansetron, granisetron and tropisetron are highly specific for the 5-HT3 receptor and have a selectivity ratio of approximately 1000:1 compared with affinities for other receptors. Other 5-HT3 receptor antagonists, largely those having a benzamide structure, are non-selective. These include metoclopramide, renzapride and zacopride which stimulate gastric motility via activation of 5-HT4 receptors; metoclopramide is also a potent dopamine receptor antagonist. Selective 5-HT3 receptor antagonists are a major advance in the treatment of chemotherapy- and radiotherapy-induced emesis in cancer patients. These agents inhibit emesis by blocking 5-HT3 receptors on vagal afferent nerve terminals in the gastrointestinal mucosa and on terminals on the same vagal nerves in the vomiting system. Inhibition of acute emesis appears to be produced by blocking the initiation of the emetic reflex induced via 5-HT3 receptors and by 5-HT released from enterochromaffin cells in the small intestine, as well as by blocking 5-HT3 receptors in the hindbrain vomiting system.
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PMID:Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action. 152 96

A series of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]benzamides (11-64) were prepared and evaluated for gastrokinetic activity by determining their effects on the gastric emptying of phenol red semisolid meal in rats. The N-4 substituent includes alkyl, phenoxyalkyl, (4-fluorobenzoyl)alkyl, and heteroarylmethyl groups. The benzamide derivatives, having an isopropyl, isoamyl, neopentyl, 3-(4-chlorophenoxy)-propyl, or pyridylmethyl group at N-4, showed potent in vivo gastric emptying activity. In particular, 4-amino-5-chloro-2-ethoxy-N-[[4-(3-pyridylmethyl)-2- morpholinyl]methyl]benzamide (57b) was equipotent to the 4-fluorobenzyl analogue 1b (AS-4370 as its citrate) in the gastrokinetic activity on phenol red semisolid meal in rats and mice, and on resin pellet solid meal in rats. Moreover, compound 57b was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests. Structure-activity relationships of compounds with various substituents at N-4 are also discussed.
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PMID:Novel benzamides as selective and potent gastrokinetic agents. III. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]-benzamides. 153 91

Alizapride (ALZ) is a new benzamide derivative with promising antiemetic activity. In the present study, high-dose ALZ (16 mg/kg) alone or in combination with dexamethasone (DXM, 40 mg) was compared to a combination of DXM (40 mg) and metoclopramide (MCP, 4 mg/kg) in a randomized cross-over trial conducted on 21 out-patients at high emetic risk after moderate-dose cisplatin. All but 3 patients completed the planned cross-over trial for a total of 60 evaluable courses. The patients completed a self assessment questionnaire evaluating the severity and duration of both nausea and vomiting, the toxicity, as well as their subjective opinion of the antiemetic trial. At the dose and schedule employed, ALZ alone or in combination with DXM provided not only a significantly lower rate of complete protection against nausea and vomiting (0 and 4.8%) than MCP + DXM (28.6%) but was also less effective in reducing the number of vomiting episodes and the duration of the vomiting. In addition, the MCP - DXM regimen was the most frequently preferred. Except for one case of orthostatic hypotension following ALZ, benzamide-induced toxicity was mild, whereas that related to DXM was negligible. The results of this study suggest that high-dose ALZ gives no advantage compared to MCP in patients at high risk for emesis after moderate-dose cisplatin.
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PMID:Alizapride alone or alizapride-dexamethasone compared with metoclopramide-dexamethasone in patients at high risk of acute emesis after cisplatin. A randomized cross-over study. 195 93

The title compounds (19-55) with a 4-substituted 2-(aminomethyl)morpholine group were prepared and evaluated for the gastrokinetic activity by determining their effect on gastric emptying of phenol red semisolid meal in rats. Introduction of chloro, fluoro, and trifluoromethyl groups to the benzyl group of the parent compounds 1a and 1b enhanced the activity. Among compounds tested, 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl] methyl] benzamide (23b) showed the most potent gastric emptying activity (effects on phenol red semisolid meal in rats and mice, and on resin pellets solid meal in rats). The gastrokinetic activity of 23b citrate (AS-4370) compared very favorably with that of cisapride and was higher than that of metoclopramide. In contrast to metoclopramide and cisapride, AS-4370 was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests.
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PMID:Novel benzamides as selective and potent gastrokinetic agents. 2. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2- morpholinyl]methyl] benzamide citrate (AS-4370) and related compounds. 199 85

Drugs that enhance gastrointestinal motility include the benzamide drugs metoclopramide, cisapride and renzapride (BRL-24924). Because these agents also are serotonin-3 (5-HT3) receptor antagonists, which can promote gastric emptying in some species, the motor-stimulating properties of benzamide agents may be due to this mechanism. Metoclopramide (0.3-3.0 mg/kg i.v.), cisapride (0.03-1.0 mg/kg i.v.) and BRL-24924 (0.01-0.1 mg/kg i.v.) were evaluated for their relative motility-stimulating and 5-HT3 receptor antagonist activities in conscious dogs and were compared with selective 5-HT3 antagonist antiemetic compounds ICS-205-930, (3 alpha-tropanyl)1-H-indole-3-carboxylic acid ester and granisetron (BRL-43694). Gastric antral contractions and intestinal myoelectric motility were determined in response to drugs, as were their effects on solid and liquid emptying in a gamma scintigraphic model of gastroparesis. 5-HT3 receptor antagonist potency was examined by deriving ED50 values for inhibition of cisplatin emesis. All drugs were 5-HT3 antagonists as they blocked cisplatin emesis with relative potencies of BRL-43694 = ICS-205-930 greater than BRL-24924 greater than cisapride = metoclopramide. The order of potency for stimulating fasted dog antral contractile activity, however, was BRL-24924 = cisapride greater than metoclopramide greater than ICS-205-930 = BRL-43694. Maximally effective doses of BRL-24924 (0.1 mg/kg i.v.) and cisapride (0.67 mg/kg i.v.) in the antrum also stimulated intestinal myoelectrical activity, whereas ICS-205-930 (0.5 and 2.0 mg/kg i.v.) was not active.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of serotonin-3 receptor antagonist activity to gastric emptying and motor-stimulating actions of prokinetic drugs in dogs. 207 88

Levo-sulpiride is a substituted benzamide with antiemetic activity 3-8 times more potent than the racemic form and the d-isomer. Its mode of action is partially central (inhibition of dopaminergic receptors at the trigger zone for vomiting) and partially peripheral (normalization of motor activity of stomach and gall-bladder). The drug was found effective in the prevention of chemotherapy-induced and post-operative vomiting as well as in the treatment of nausea and vomiting during hepatic, biliary and gastroduodenal disorders, organic and functional dyspepsia, motion sickness and vertigo. Levo-sulpiride is at least as effective as domperidone, antihistamines and neuroleptic agents. Compared with the latter drugs and with d-sulpiride and the racemus, l-sulpiride is much better tolerated. Drowsiness is reported only at high doses, and no clinical signs of hyperprolactinaemia are observed, even after prolonged treatment.
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PMID:[Antiemetic properties of levo-sulpiride]. 228 Aug 76

1. The aim of this study is to review the mechanisms implicated in nausea and vomiting and the treatment of these symptoms. 2. Metoclopramide, a benzamide, is the drug most frequently used to alleviate or abolish the majority of nausea and vomiting of different origin. Domperidone, which scarcely penetrates the central nervous system (CNS), is less used. 3. The treatment of vomiting induced by cytotoxic drugs is necessary to use a combination (two or more) of antiemetic drugs (metoclopramide, glucocorticoids, antihistamines, butyrophenones, anticholinergics, cannabinoids). Recently, antagonists of serotonergic (5-HT) receptors of the subtype 5-HT3 appear to possess interesting antiemetic properties and they have a promising future in this field. 4. Antagonists of dopamine receptors (benzamides, phenotiazines, butyrophenones and domperidone) induce adverse reactions in CNS (mainly extrapyramidal disorders), which are scarce with metoclopramide and practically absent with domperidone. These disorders must not suppress antiemetic therapy when it is needed.
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PMID:Therapeutic management of nausea and vomiting. 240 30

The antiemetic effect of a new benzamide, alizapride, was investigated with escalating doses through four levels starting at 5 mg/kg/cycle up to 20 mg/kg/cycle. 39 patients were accrued who received cancer chemotherapy which included the following drugs in various combinations: cyclophosphamide, adriamycin, fluorouracil, carboplatin and etoposide (VP-16). Complete control of emesis was achieved in a third of the 39 patients. There was no statistically significant difference among the dose levels with regard to the patient's assessment of the incidence and severity of nausea and vomiting. Alizapride was well tolerated at all dose levels tested with minimal toxicity. Mild sedation was reported in 60% of the patients. Neither extrapyramidal reactions nor hypotensive side effects were observed. Thus the therapeutic yield of alizapride could be further studied concerning the optimal dose and schedule as well as its use in combination with other antiemetic drugs.
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PMID:Antiemetic efficacy of escalating doses of alizapride against chemotherapy-induced emesis. 274 66


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