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)

The antiemetic effects of the benzamide metoclopramide (MCL, Paspertin) and of the butyrophenone droperidol (DRO, Dehydrobenzperidol) were compared by two sequential analytical trials in cisplatin treated patients. In the first trial (cisplatin 60-90 mg/m2) the drugs were given as loading infusions (MCL 0.5 mg/kg, and DRO 0.05 mg/kg, each per b.w./h over 2 hr), beginning 2 hr before cisplatin administration; this was followed by the maintenance infusion at half the dose, over 24 hr (total dose of MCL 7 mg/kg, and DRO 0.7 mg/kg b.w. per cycle, resp.). During the second trial (cisplatin 90-120 mg/m2) the antiemetic dosages were doubled (total dose of 14 or 1.4 mg/kg per cycle. After 12 and 14 treatment pairs, resp., MCL was significantly (P less than 0.05) more effective than DRO. Clinically antiemetic protection (i.e. less than three vomiting episodes) were seen in 9 of 12 and 13 of 14 patients, resp., compared with only 5 of 12 and 5 of 14 patients on DRO. The incidence of major extrapyramidal side-effects was more than 2-fold higher at DRO. The benefit/risk relationships (i.e. the relation between the prevented emetic episodes and the number of extrapyramidal reactions seen) of MCL were 2.7-3.0-fold better than those of DRO. The relatively higher antiemetic efficacy of MCL may be due to its additional gastrointestinal mechanisms.
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PMID:High doses of metoclopramide or droperidol in the prevention of cisplatin-induced emesis. 354 51

The antiemetic effect of two benzamides, metoclopramide (MCL; Paspertin) and alizapride (AZP; Vergentan), was compared in two double-blind sequential analytical trials in cisplatin-treated patients (60-90 mg/m2). In the first trial, the drugs were given as loading infusions (0.5 mg/kg of body weight/hour over 2 hours) beginning 2 hours before cisplatin administration; the maintenance infusion (0.25 mg/kg/hour) given over 24 hours was half the dose (total dose, 7 mg/kg of body weight per treatment cycle). In the second trial, the dose of AZP was doubled. After nine and ten treatment pairs, MCL was significantly (2P less than 0.10) more effective than AZP: three of nine and four of ten patients receiving MCL remained totally free from vomiting, compared with only none of nine and one of ten patients receiving AZP. The incidence of extrapyramidal reactions was similar in all treatments. However, the administration of AZP was much more unfavorable because of moderate to severe hypotensive side effects.
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PMID:Comparison of the antiemetic efficacy of two high-dose benzamides, metoclopramide and alizapride, against cisplatin-induced emesis. 391 40

The antiemetic efficacy of metoclopramide (MCL, Paspertin, loading infusion 0.5 mg/kg body wt./h over 2 h, maintenance infusion 0.25 mg/kg/h over 24 h) has been compared with haloperidol (HAL, Haldol, 1/10 of MCL dosage) and with triflupromazine (TFP, Psyquil, 1/2 of MCL dosage) in two sequential analyses, against the emetic effects of cisplatin (60-90 mg/m2). After treating 14 and 8 pairs of patients respectively, MCL was significantly (alpha = 0.05) more effective than HAL or TFP. Only 1 of the 14 patients in the HAL group and 0 of 8 in the TFP group were totally protected against emesis, in contrast to 6 of 14 patients and 3 of 8 in the MCL groups. In order to quantify the benefit/risk relationship of the antiemetic drugs studied the number of prevented emetic episodes (in comparison to previous insufficient treatment) was related to the incidence of major undesired effects (i.e. dystonia and/or akathisia). This relationship was 17.8 and 12.1 for the two MCL groups; for HAL and TFP it was only 5.8 and 4.6, respectively. The high antiemetic selectivity of MCL against cisplatin-induced emesis is probably related to the still unknown action of MCL on the gastrointestinal motility. A high neuroleptic potency, with or without additional anticholinergic activity, is apparently not essential for high antiemetic protection against cisplatin.
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PMID:[Benefit and risk of high-dose metoclopramide in comparison to high-dose haloperidol or triflupromazine in cisplatin-induced vomiting]. 403 75

The antiemetic effect of oral medium-dosed metoclopramide (MCL, 3.5 mg/kg b.w./cycle) and placebo for chemotherapy-induced emesis of a noncisplatin regimen was assessed for inpatients and outpatients in two double-blind placebo-controlled sequential analyses according to Bross (1952). MCL was given in 5 single doses of 0.7 mg/kg b.w. at 0 h (loading) and at 2 h (i.e. start of chemotherapy) and 6, 10 and 14 h (as maintenance doses). Both studies ended after 8 sequential pairs in favor of MCL (2 alpha = 2 beta = 0.05). Major antiemetic protection (< 2 emetic episodes per 26 h) was achieved for 8/8 of inpatients and 7/8 of outpatients (placebo 0/8 and 0/8). Side effects neither required discontinuation of the antiemetic regimen nor additional therapy. The median of MCL plasma levels ranged from 150 to 750 ng/ml and terminal half-lives from 3.9 to 8.9 h.
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PMID:Oral medium-dosed metoclopramide versus placebo as highly effective antiemetic prophylaxis in in- and outpatients on noncisplatin chemotherapy. 845 Oct 40

kappa-Opioid agonists may functionally antagonize some behavioral effects of cocaine, but the role of mixed kappa/mu receptor activity is unclear. The effects of three mixed kappa/mu agonists (MCL-101, (-)cyclorphan, and Mr2034) and one kappa-selective agonist (enadoline) on cocaine self-administration and cocaine discrimination were compared in rhesus monkeys. Acute treatment with all kappa agonists dose dependently reduced cocaine-maintained responding and produced a downward shift in the cocaine self-administration dose-effect curve (0.001-0.32 mg/kg/inj, i.v.). During 7 days of chronic treatment, (-)cyclorphan (0.0032-0.032 mg/kg/h) and MCL-101 (0.0032-0.032 mg/kg/h) each dose dependently reduced cocaine self-administration maintained by a dose near the peak of the cocaine self-administration dose-effect curve. MCL-101 (0.032 mg/kg/h) produced selective and sustained decreases in cocaine self-administration, whereas (-)cyclorphan (0.032 mg/kg/h) had selective but transient effects. In addition, these mixed kappa/mu agonists produced fewer side effects (some salivation) than the kappa-selective agonist (sedation, salivation, emesis). However, none of these kappa agonists substituted for or antagonized cocaine's discriminative stimulus effects in monkeys trained to discriminate cocaine (0.4 mg/kg, i.m.) from saline. Thus, kappa and mixed kappa/mu-opioid agonists may reduce cocaine self-administration without altering cocaine's discriminative stimulus effects. Mixed kappa/mu agonists appear to offer some advantages over selective kappa agonists as potential treatments for cocaine abuse.
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PMID:Effects of mixed-action kappa/mu opioids on cocaine self-administration and cocaine discrimination by rhesus monkeys. 1263 53