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Cortical spreading depression (CSD) was used to model migraine in adult male Wistar rats. Five CSDs were induced by pinprick. Metoclopramide (two different doses), raclopride, or 0.9% saline were administered 30 min before CSD induction. Two hours after the experiments, brain tissues were examined for c-fos activation.
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The catecholamine (CA) response to upright posture was studied in 30 brainstem infarct patients with orthostatic arterial hypotension; the investigation was made before and after 10 days propranolol therapy (in 15 cases) and before and after 10 days metoclopramide therapy (in other 15 cases). Before treatment almost all patients responded to posture by a rise in adrenaline (A) excretion and by a depression in noradrenaline (NA) excretion. Propranolol therapy prevented the excessive A release produced by standing and normalized their NA response to posture. Metoclopramide administration also prevented the post-orthostatic A discharge but had no significant influence on NA response to posture. Both drugs exerted a favourable influence on postural hypotension of investigated patients. As post-orthostatic A discharge observed in patients with postural hypotension is involved in the pathogeny of this syndrome and both metoclopramide and propranolol are able to correct this disorder one may maintain that the clinical favourable results obtained with these drugs are ascribable at least partly to their blocking effect on A release.
Postradioiodine nausea and vomiting within three days of therapy (primary endpoint); occurrence of adverse reaction.
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A combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS + MTC) was compared with oral sumatriptan (100 mg) and placebo in 421 patients with migraine in a randomized, double-blind, clinical trial. LAS + MTC was as effective as sumatriptan with a decrease in headache from severe or moderate to mild or none in 57% and 53%, respectively, for the first migraine attack treated, the primary efficacy parameter. Both treatments were better than placebo (success rate 24%, p < 0.001). LAS + MTC was better tolerated than sumatriptan (adverse events in 18% and 28%, respectively, p < 0.05).
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The purpose of this study was to compare the relative severity of nausea and vomiting scores before and after initiation of treatnment regimens in end-of-life cancer patients, and secondarily to evaluate the efficacy of a combination antiemetic preparation (ABHR; lorazepam [Ativan], diphenhydramine [Benadryl], haloperidol [Haldol], and metoclopramide [Reglan] in this patient population. A retrospective analysis of antiemetic use was performed through a systematic chart review of patients with an end-of-life diagnosis of lung, pancreatic, or colorectal cancer whose medications were provided through Hospice Pharmacia. Information collected included patient age and sex; terminal diagnosis; pre- and post-antiemetic nausea and vomiting scores; and initial antiemetic choice. A total of 584 patient records were examined, and the most widely used antiemetics used were prochlorperazine, metoclopramide, and ABHR. The most prevalent diagnosis was lung cancer. All of the agents and preparations were determined to be effective as intial therapy for the management of nausea and vomiting in the end-of-life cancer patient; therefore use of these agents as first-line therapy options in this population appears to be justified. ABHR appears to be at least as efficacious as other first-line monotherapy options investigated. Despite a lack of information on the absolute bioavailability of alternative ABHR dosage forms such as suppositories and topical gels, these also appear to be efficacious and therefore are viable options in the treatment of nausea and vomiting in end-of-life cancer patients.
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We describe the clinical course of a 25-years-old female patient, who presented with massive orofacial tardive dsykinesia after therapy with metoclopramide (MCP). She had stapedectomy in general anaesthesia and suffered from PONV. The dyskinesia was treated successfully with Biperiden 5 mg i. v.
A combination of experimental and theoretical methods were used to investigate the stereoelectronic structure of zetidoline, a dopamine D2 receptor antagonist showing Na+-dependent binding. The solid-state conformation of zetidoline is characterized by synplanarity (coplanarity of the two rings with the chloro substituent and the carbonyl group on the same side). The side chain in the crystal adopts a folded conformation which places the azetidine nitrogen atom at about 8 A from the center of the aromatic ring. Quantum mechanical calculations indicate the synperiplanar and antiperiplanar conformations of the ring system to be of approximately equal energies. The molecular electrostatic potential of zetidoline in a nearly extended conformation shows a remarkable similarity with that of orthopramides (e.g. metoclopramide) and indolones (e.g. piquindone), i.e. two groups of drugs displaying the same D2 selectivity and Na+-dependent binding. We postulate that the close stereoelectronic similarity between zetidoline, orthopramides, and indolones accounts for their identical mechanism of action in the molecular level.
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The small number of included trials provided some, albeit weak and unreliable, evidence which appeared to favor the use of ondansetron and metoclopramide over placebo to reduce the number of episodes of vomiting due to gastroenteritis in children. The increased incidence of diarrhea noted with both ondansetron and metoclopramide was considered to be as a result of retention of fluids and toxins that would otherwise have been eliminated through the process of vomiting.
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A total of 100 women (mean [SD] age, 52  years; height, 154  cm; weight, 54  kg) were included in the study. Each study group comprised 25 patients. There were no significant differences between treatment groups with regard to patient demographics, surgery type, or awakening time. The prevalences of PONV 0 to 24 hours after anesthesia were 28% with propofol (P = 0.005), 32% with droperidol (P = 0.011), and 60% with metoclopramide (P = NS), compared with placebo (68%). No significant difference in the prevalence of PONV was found between patients receiving propofol and those receiving droperidol, and propofol and droperidol were associated with significantly lower prevalences of PONV compared with metoclopramide (P = 0.022 and P = 0.043, respectively). Extrapyramidal symptoms were not reported in any of the groups.
The intravenous injection of cisplatin in the ferret caused a consistent emetic (vomiting/retching) response. Emesis induced by cisplatin was abolished by the 5-hydroxytryptamine (5-HT) M-receptor antagonists ICS205-930, zacopride, dazopride and metoclopramide. The neuroleptic agents haloperidol, fluphenazine, domperidone, sulpiride and tiapride also antagonized emesis induced by cisplatin but only a proportion of the animals were completely protected and diazepam and prednisolone only reduced the intensity of the response. It is concluded that compounds used in the clinic to antagonise emesis induced by chemotherapy are effective in the ferret model. Antagonism of emesis induced by cisplatin in the ferret was most potently achieved by the use of the 5-HT M-receptor antagonists ICS205-930 and zacopride. However, an antagonism of dopamine receptors would appear relevant to the anti-emetic effects of the neuroleptic agents and may contribute to the anti-emetic effects of metoclopramide. Diazepam and prednisolone exert their modest antagonism by unknown mechanisms. The use of the 5-HT M-receptor antagonists is revealed as a novel approach to the treatment of emesis induced by cisplatin.
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A retrospective, cross- sectional observational study involving 823 consecutive elective patients for diagnostic gynaecological laparoscopic procedures. The 823 patients were classified as American society of Anesthesiologists (ASA) I or II patients and were studied over the fifteen year period. They were all premedicated with atropine & metoclopramide after overnight fast, and had general anaesthesia by facemask with assisted ventilation; using thiopentone for induction, paracetamol & piroxicam for analgesia and oxygen-halothane via Bain's breathing circuit for maintenance. Monitoring procedures employed in this study included pulse rate (PR), non-invasive blood pressure (NIBP) and oxygen saturation (SPO2).
Spermiation and changes in androgen (testosterone, T and 11-ketotestosterone, 11-KT) levels were studied in sterlet (Acipenser ruthenus) treated with GnRH agonist implants (DAla(6)-Pro(9)-LHRHa) at 25 and 75 μg kg(-1) b.w. and compared with those males treated with 4 mg kg(-1) b.w. of carp pituitary extract (CPE) and 3 pellets of Ovopel kg(-1) b.w., which contains DAla(6)-Pro(9)NEt-mGnRH and metoclopramide. Sperm quality (sperm mass, spermatozoa concentration and sperm motility and velocity) was evaluated 24, 48 and 72 h after hormonal treatments. Males did not release sperm in the control group injected with physiological solution, while sperm could not be collected 7 days after treatments in all hormonally treated groups. Spermiation rates were 100 % in the CPE and Ovopel groups and 25-50 % in the GnRHa-treated groups. Sperm production was significantly lower in the GnRHa-treated groups than in the CPE and Ovopel groups and decreased 72 h after hormonal treatment. Sperm motility and velocity were higher in the Ovopel and GnRHa (75 μg) groups compared to the CPE and GnRHa (25 μg) groups and decreased 72 h after hormonal treatment. Androgens were only affected in spermiating males and changed in the Ovopel and GnRHa (75 μg) after hormonal treatment. Significant correlations were observed between sperm production, sperm motility and sperm velocity, but not androgens. The present study suggests involvement of dopamine in sturgeon spawning. Additionally, better sperm quality observed in the Ovopel group and particularly sperm motility in the GnRHa (75 μg) suggests enhancement of sperm quality in sturgeon treated with GnRHa. Therefore, further study is needed to induce fully spermiation using GnRHa implants in combination with a dopamine inhibitor.
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Gastroparesis from numerous causes has been treated with a number of prokinetic agents. We report the successful use of erythromycin as a prokinetic agent in the treatment of two cases of idiopathic gastroparesis in which treatment with metoclopramide or domperidone or both had failed. We also review information about erythromycin's mechanism of action, previous therapeutic uses, administration (doses, duration, and route), and role as an alternative to other prokinetic agents. When treatment with other agents is unsuccessful, erythromycin is a viable alternative therapy for gastroparesis.
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Twelve articles met our inclusion criteria. Of these, 11 were prospective trials, and 5 were randomized, blinded clinical trials. Study size ranged from 6 to 77 patients. Eight studies showed patient improvement with metoclopramide in at least 1 measured outcome; 1 study showed worsening symptoms with metoclopramide. Of the 5 randomized, blinded trials, 2 showed no effect of metoclopramide on any outcome, and 2 showed a significant placebo effect. Four studies commented on adverse effects of therapy, with irritability being the most frequently reported potential adverse effect of therapy. Other reported adverse effects included dystonic reactions, drowsiness, oculogyric crisis, emesis, and apnea. Among studies, there was marked heterogeneity in the patient populations, dosing, and outcomes studied. Therefore, a meta-analysis was not performed. We both agreed on a US Preventive Service Task Force rating of "poor" for the level of evidence, leading to an "inconclusive" recommendation for the safety and efficacy of metoclopramide in infants.
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University-affiliated women's hospital.