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Dopamine (DA) causes a dose-dependent increase in the frequency of motor neuron bursts [virtual ventilation (fR)] produced by deafferented crab ventilatory pattern generators (CPGv). Domperidone, a D2-specific DA antagonist, by itself reversibly depresses fR and also blocks the stimulatory effects of DA. Serotonin (5HT) has no direct effects on this CPGv. Nicotine also causes dramatic dose-dependent increases in the frequency of motor bursts from the CPGv. The action is triphasic, beginning with an initial reversal of burst pattern typical of reversed-mode ventilation, followed by a 2- to 3-min period of depression and then a long period of elevated burst rate. Acetylcholine chloride (ACh) alone is ineffective, but in the presence of eserine is moderately stimulatory. The inhibitory effects of nicotine are only partially blocked by curare. The excitatory action of nicotine is blocked by prior perfusion of domperidone, but not by SKF-83566.HCl, a D1-specific DA antagonist. SKF-83566 had no effects on the ongoing pattern of firing. These observations support the hypothesis that dopaminergic pathways are involved in the maintenance of the CPGv rhythm and that the acceleratory effects of nicotine may involve release of DA either directly or via stimulation of atypical ACh receptors at intraganglionic sites.
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To investigate the influence of omeprazole on the pharmacokinetics of domperidone given as free base and maleate salt.
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No statistically significant differences were obtained between the two products with respect to the mean concentration-time profiles or in the pharmacokinetic parameters, including area under the serum concentration-time curve from the present study. The relative extent of absorption as assessed by the AUC ratio (Test/Reference) and C(max), the average value was found to be 1.00 +/- .09 with 90% confidence limits (C.L.) of 0.82-1.18.
The quasi-steady state current-voltage relationship from the isolated guinea pig ventricular cells were measured using whole-cell patch-clamp techniques with a slow ramp depolarization (8 mV.s-1).
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Étant donné les lacunes dans la littérature, il est recommandé que l’utilisation de dompéridone chez les patients sous dialyse soit évaluée au cas par cas. Il faut faire preuve d’énormément de prudence chez les patients qui prennent quotidiennement plus de 30 mg de ce médicament. [Treduction par l’éditeur].
(a) NMDA has a dual effect on prolactin secretion that is independent of prior prolactin concentrations and of dopamine activity, but kainic acid is only inhibitory. (b) The stimulatory or inhibitory effects of NMDA and kainic acid on PRL secretion were not strictly related to basal PRL concentrations and necessarily involved a change in the secretion of prolactin releasing factors, as no correlations were observed between changes in pituitary concentrations of dopamine and serum PRL concentrations. (c) Females rendered hyperprolactinaemic by neonatal administration of testosterone or oestradiol responded differently after NMDA administration. (d) NMDA and kainic acid blocked the mechanisms involved in stress-induced PRL secretion.
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The mean CTT was 40.71 h in patients vs 24.75 h in controls (p = 0.013). In patients, faecal loading was significantly greater than in controls (p<0.001). Bloating correlated significantly positively with CTT ( r = 0.174, p = 0.009), and faecal load. Abdominal pain correlated significantly positively with distal faecal loading ( r = 0.151; p = 0.036). The mean CTTs in patients with zero to four colon redundancies were: 36.26 h, 43.80 h, 41.65 h and 52.27 h, respectively (p = 0.030), and symptoms increased significantly with increase in the number of redundancies (p<0.001). A subgroup of patients (n = 90) with normal CTTs (< or = 24.75 h) had significantly higher faecal loading compared to controls (p = 0.033). Factor analysis showed that bloating correlated significantly with abdominal pain and defecation rate (p<0.05) and that CTT and faecal load correlated inversely with daily defecation rate, ease, incompleteness, repetitiveness, and faecal consistency. Intervention significantly reduced CTT, faecal loading, bloating, abdominal pain, and improved defecation patterns (p<0.05).
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In eight normal adult men pituitary secretion following GRF(1-40) was studied. GRF administration (50 micrograms i.v.) was followed by an increase in GH release with a peak value between the 15 and 60 min. No effects were noticed on LH, FSH, PRL, TSH and ACTH secretion. GH and PRL release was also studied after domperidone (DOM) (5 mg i.v./h), and GRF plus DOM. PRL increased significantly after DOM and GRF plus DOM. During GRF plus DOM a more marked GH release was observed in comparison with the hormone response to GRF alone at 15-45 and 120 min (P less than 0.05). This phenomenon was found in in six out of eight subjects studied. Mean peak and secretory area was greater (P less than 0.05) after GRF plus DOM than after GRF alone. These data suggest that GRF(1-40) at the dose used is a useful tool in the study of GH secretion. The GH pattern during GRF plus DOM seems to indicate that dopaminergic tone may play a direct inhibitory role on GH secretion in man.
Migraine is Europe and North America's most frequent neurological illness. Its prevalence is about 12%, affecting women twice more than men. Migraine illness is defined by the occurrence of several episodes of pulsatile headaches, uni- or bilateral, accompanied or preceded by signs of central and autonomic nervous system dysfunction. Considered benign, it can lead to non negligible social and professional handicap. Its social and economic repercussions are serious, due to consequences in terms of work incapacity. Essentially relying on drugs, therapeutic divides itself into migraine attack treatment and migraine prophylaxis. Migraine attack treatment relies essentially on acetaminophen and non-steroidal antiinflammatory agents, associated or not with antiemetics like domperidone and metoclopramide, accessorily on ergot derivatives and triptans. Migraine prophylaxis is best provided by propranolol, valproic acid and amitryptiline, anti-serotoninergic agents, topiramate, flunarizine and other agents should be reserved to particular cases. In some cases, children in particular, non-drug approaches such as relaxation, biofeedback or behavioral therapy can be privileged although relying on weak scientific evidences.
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The influence of Motilium (domperidone) tablet on the increase of human prolactin level was investigated in the first and second trimester of pregnancy, in confinement and menopause. It has been stated that domperidone causes the serum prolactin level to increase not only in pregnancy and confinement but in menopause, too, not depending on whether it was spontaneous or it took place after castration. In spite of the fact that domperidone is a dopamine antagonist it increases the FSH level similarly to bromocriptine which is a dopamine agonist, although the serum prolactin level changes in the opposite direction on the effect of the treatment. The decrease of the prolactin level effected by bromocriptine tablet in physiological and pathological galactorrhoea and in hyperprolactinaemia associated with infertility has also been investigated. In addition to the favourable laboratory and clinical results it has been stated that prolactin regulates the changes of the FSH and LH levels both in fertility and menopause.
A 47-year-old woman with diabetic gastroparesis, on treatment with domperidone, a dopamine-receptor antagonist, was admitted to the hospital in coma, with high blood pressure and nonreactive pupils. She then developed high fever. Her condition progressively worsened for two days, when muscle rigidity was noted and creatine phosphokinase was greater than 2000 U/liter. A diagnosis of neuroleptic malignant syndrome was made, and the patient was given dantrolene with prompt and complete resolution of all signs and symptoms. Subsequent inquiry revealed a distant past history of positive muscle biopsy for malignant hyperthermia, obtained after the diagnosis had been made in a family member. This case suggests that domperidone may induce neuroleptic malignant syndrome and that patients with malignant hyperthermia are at increased risk for this complication.
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In ruminants, the dopaminergic regulation of feeding behaviour has not been investigated. Therefore, the effects of dopamine receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats. Goats treated i.v. with bromocriptine (1 micrograms or 2.5 micrograms/kg body wt/min during 10 min) ate less food than when treated with saline. This inhibitory effect on food intake could not be prevented by the peripheral dopamine receptor antagonist domperidone (0.5 mg/kg body wt i.v.). In contrast, dopamine (i.v. 20 micrograms/kg body wt/min during 15 min), levodopa (i.v. 40 micrograms/kg body weight during 10 min), apomorphine (i.v. 2 micrograms/kg body wt/min during 10 min) and lisuride (i.v. 0.2 microgram/kg body wt/min during 15 min and 0.5 microgram/kg body wt during 10 min) failed to modify food intake. Given in association with benserazide, a decarboxylase inhibitor (i.v. 20 micrograms/kg body wt/min during 10 min), levodopa was still inactive as an anorectic agent. Levodopa, bromocriptine and lisuride administered at similar dose rates to those which were used in the food intake experiments, induced some clinical signs including inhibition of forestomach contractions. The inhibition of rumen contractions induced by these drugs was completely antagonized by domperidone pretreatment. These results, together with earlier in vivo and in vitro observations, suggest that the inhibitory effects of dopamine receptor agonists on forestomach contractions are due to interactions with peripheral dopaminergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, probably does not modify feeding behaviour in dwarf goats.(ABSTRACT TRUNCATED AT 250 WORDS)
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We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc.
To study the short-term influences of pharmacologic hyperprolactinemia on hydrocortisone (HC)-induced effects on selected immune parameters.
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Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment).
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Whether an additional Braun enteroenterostomy is necessary in reducing delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) has not yet been well investigated. Herein, in this retrospective study, 395 consecutive cases of patients undergoing classic PD from 2009 to 2013 were reviewed. Patients with and without Braun enteroenterostomy were compared in preoperative baseline characteristics, surgical procedure, postoperative diagnosis, and morbidity including DGE. The DGE was defined and classified by the International Study Group of Pancreatic Surgery recommendation. The incidence of DGE was similar in patients with or without Braun enteroenterostomy following PD (37/347, 10.7% vs 8/48, 16.7%, P = 0.220). The patients in the 2 groups were not different in patient characteristics, lesions, surgical procedure, or postoperative complications, although patients without Braun enteroenterostomy more frequently presented postoperative vomiting than those with Braun enteroenterostomy (33.3% vs 15.3%, P = 0.002). Bile leakage, pancreatic fistula, and intraperitoneal abscess were risk factors for postoperative DGE (all P < 0.05). Prokinetic agents and acupuncture were effective in symptom relief of DGE in 24 out of 45 patients and 12 out of 14 patients, respectively.The additional Braun enteroenterostomy following classic PD was not associated with a decreased rate of DGE. Postoperative abdominal complications were strongly correlated with the onset of DGE. Prokinetic agents and acupuncture could be utilized in some patients with DGE.
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Acupuncture at the acupoints selected by pattern/syndrome differentiation and domperidone are effective in the treatment of functional dyspepsia. Domperidone is unsatisfactory in the long-term effect, but acupuncture achieves the positive short-term and long-term effects on functional dyspepsia.
This unexpected finding suggests that dopaminergic neurons outside of the blood-brain barrier may be important in restless legs syndrome pathophysiology.
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Prospective controlled trials evaluating medication use in children with vomiting from gastroenteritis.
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To investigate the effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease (GERD).
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Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips.
A liquid chromatographic-mass spectrometric (LC-MS) method has been developed and validated for simultaneous determination of dehydroevodiamine and limonin from Evodia rutaecarpa in rat plasma. After addition of the internal standard, domperidone, plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on an Apollo C(18) column (250 mm × 4.6 mm, 5 μm), with methanol-0.01% formic acid water (60:40, v/v) as mobile phase, within a runtime of 12.0 min. The analytes were detected without interference in the selected ion monitoring (SIM) mode with positive electrospray ionization. The linear range was 1.0-500 ng mL(-1) for dehydroevodiamine and 2.0-1,000 ng mL(-1) for limonin, with lower limits of quantitation of 1.0 and 2.0 ng mL(-1), respectively. Intra-day and inter-day precision were within 6.0% and 10.9%, respectively, for both analytes, and the accuracy (relative error, RE, %) was less than 4.8% and 6.5%, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of dehydroevodiamine and limonin in rat plasma after oral administration of dehydroevodiamine, limonin, and an aqueous extract of Evodiae fructus. The results indicated there were obvious differences between the pharmacokinetic behavior after oral administration of an aqueous extract of Evodiae fructus compared with single substances.
Accurate diagnosis of gastroparesis requires an adequate protocol to measure gastric emptying. Treatment options in gastroparesis remain limited despite the disabling nature of the disorder.
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45 (34.6%) gastroesophageal reflux disease were found in 130 cases. 21 cases(91.3%) were healed in group A. 3 of 22 cases (13.6%) were healed in control (P < 0.01).