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In prolactinoma patients, the unresponsiveness of prolactin (PRL) to dynamic tests with thyrotropin-releasing hormone (TRH) or dopamine agonist or antagonist drugs suggests that the disease is caused by the failure of central dopaminergic inhibition. The absence of PRL secretory response to dopamine or TRH in prolactinoma patients also may be an effect of the disease. Twenty-six women diagnosed by dynamic tests and radiologic examination as having PRL-secreting adenoma were treated surgically (15) or with bromocriptine (11) and their condition was evaluated one to three years later by TRH, nomifensine, and domperidone tests. Basal PRL levels decreased after surgery and bromocriptine treatment. At the time of the follow-up study, PRL levels were elevated in six of the 15 surgically treated patients and in six of the 11 treated with bromocriptine. Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients. These results indicate that the alteration of TRH or dopaminergic receptors in the regulation of PRL secretion in prolactinoma is related to the disease and disappears when the tumor is removed or treated successfully with bromocriptine.
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Immersion of one hand into ice water (cold pressor test) in eight hypertensive subjects induces elevation of mean arterial pressure, increase in heart rate, and no significant changes of plasma renin activity and plasma aldosterone concentrations. Domperidone, a DA2 dopaminergic antagonist, attenuates heart rate increase induced by the cold pressor test, and the combination of bromocriptine, a known DA2 dopaminergic agonist, with domperidone again provoked a heart rate increase during the cold pressor test. Domperidone caused an increase of both plasma renin activity and plasma aldosterone concentrations, which were reversed by bromocriptine. These results suggest that a dopamine-receptor stimulation is taking place during the cold pressor test.
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An alteration of the hypothalamic dopaminergic regulation of LH secretion has been implicated in the abnormal LH secretion of polycystic ovarian syndrome (PCOS). To investigate this, the acute effect of dopamine (DA) receptor blockade on LH, FSH, PRL and TSH secretion was determined. No effect was observed on either LH or FSH secretion in the PCOS patients or in normal women and LH pulsatility appeared to be maintained. When the PCOS patients were divided into those who ovulated in the preceding cycle and those who were anovulatory, it was observed that the ovulatory patients had a normal PRL and TSH response; whereas in the anovulatory patients, the PRL rise was blunted and the TSH response was absent. We conclude that this study gives no evidence to support the hypothesis of altered hypothalamic DA regulation of LH secretion in PCOS. The lack of LH response to DA blockade suggests that a physiological role of DA in the control of LH secretion seems unlikely as determined under these experimental conditions. The differences in PRL and TRH response may reflect anovulation rather than a fundamental abnormality in PCOS.
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Plasma samples were processed by liquid-liquid extraction and a liquid chromatographic-mass spectrometric assay was developed for the determination of domperidone in human plasma.
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The ascertainment of sudden cardiac death (SCD) in electronic health databases is challenging.
To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients.
In all, 30 out of a total of 38 departments participated; and among those, 93% offered some form of breastfeeding education. 50% used either metoclopramide or syntocinon to promote lactation. None used domperidone. 73% had a local clinical guideline. 77% offered sessions with a lactation consultant.
Apomorphine is a potent dopaminergic agonist that quickly and predictably reverts parkinsonian symptomatology. In 32 patients (18 male) aged 45 to 83 years old (22 with idiopathic parkinsonism and 10 with parkinsonism of other causes), the dopaminergic response to apomorphine after domperidone administration was assessed using the digital skill test and Webster scale. Twenty patients with idiopathic parkinsonism and 1 with parkinsonism of other causes had a positive response to apomorphine. In 44% apomorphine had adverse effects. All patients with idiopathic parkinsonism and the only patient with parkinsonism of other causes with a positive apomorphine test had a good response to levodopa therapy. It is concluded that apomorphine test has a 95% positive predictive value for idiopathic parkinsonism and is a useful diagnostic tool.
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The effects of an oral treatment with domperidone on the gastric motor function were investigated in a double-blind study, including 129 patients, referred to the department of radiology for barium meal examination. None of them had an organic obstruction or had had previous gastrointestinal surgery. The patients received either domperidone (50, 20 or 10 mg), metoclopramide (20 mg) or a placebo. The medication was given 30 min before the intake of the barium meal in order to stimulate therapeutic conditions. During the barium meal examination, an assessment was made of the peristaltic activity of the antrum, the gastric emptying and the small bowel transit time. As to these parameters, 50 mg and 20 mg domperidone and 20 mg metoclopramide were significantly superior to the placebo.
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The physiological roles of sympathetic nerve system in the stomach has been thought to be very important in the pathogenesis of peptic ulceration. The aim of this study was to examine the effects of dopamine receptor agonists and antagonists on gastric acid secretion and gastroduodenal ulcer formation induced by cysteamine injection in rats. Cysteamine was given by subcutaneous injection as 400mg/kg in doses. Dopamine was given by continuous iv infusion as 2, 4 and 8 micrograms/kg/min in doses. Domperidone regarded as antagonists of D2 receptor was given by continuous iv infusion as 2 micrograms/kg/min in doses. As a result of acid output measured during infusion of dopamine alone or dopamine with domperidone in non-vagotomized or vagotomized rats, increasing effects of dopamine on acid output were depended on dopaminergic mechanism, and decreasing effects of dopamine on acid output were depended on dopaminergic mechanism in rami vagus. As a result of duodenal and gastric ulcer index, ulcerogenicity of cysteamine in the stomach was concerned with dopaminergic mechanism more than that of in the duodenum. These results suggested that the pathogenesis of experimental ulcer induced by cysteamine injection was depended on dopamine receptor in the stomach.
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Since results with using sulpiride and domperidone are conflicting and since both have not been tested at the same time, the aim of this study was to compare the efficacy of these substances for the induction of ovulation in deep anestrous mares in the same experimental conditions and to determine their fertility after artificial insemination (AI) at the induced estrus. Twenty-six non-pregnant, non-lactating standardbred anestrous mares were randomly assigned to three groups and treated daily for 25 days (from February 3rd to February 28th) with either sulpiride (1mg/kg of body weight im SID, n=10), or domperidone (1mg/kg po SID, n=10); 6 animals were used as control. The beginning of the transition period and the first ovulation were hastened in sulpiride (16.4+/-0.8 days) but not in domperidone (46.0+/-3.3 days) treated mares (P<0.05). The diameter of the largest follicle was affected by treatment, time and interaction of treatment-by-day (P<0.05) and significantly increased in the sulpiride group (P<0.05). Although a main effect of treatment on plasma LH concentration was not observed (P=0.06), time and interaction of treatment-by-day were statistically significant (P<0.05). The interval from the beginning of treatment to first ovulation was shorter (P<0.05) in the sulpiride group (36.9+/-2.5 days) than in the domperidone (74.7+/-3.3 days) and control (81.4+/-3.1) groups. The establishment of pregnancy was significantly (P<0.05) hastened in sulpiride (61.0+/-35.2 days) but not in domperidone (83.0+/-44.0 days) treated mares. Treated mares not pregnant after the first AI, showed normal estrous cycles with regular interovulatory intervals (P>0.05). It was concluded that sulpiride is effective in advancing the beginning of transition period and the first ovulation whereas domperidone is successful only in some mares.
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Ninety patients with CG were randomly divided into 3 groups: the control group treated with domperidone 10 mg, 3 times per day orally, the high and low-dose JWC groups treated with JWC 160 mg and 80 mg respectively 3 times per day. The therapeutic course for all groups was 14 days. Dyspeptic symptom score, gastric emptying rate and quality of life (QOL) in patients were observed.
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To perform a systematic review and meta-analysis to determine whether taking antiemetic drugs reduces vomiting and decreases the need for further intervention in children with gastroenteritis without causing significant adverse effects.
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To study the effect of dopamine receptor antagonists on anoxia-induced inhibition of Ca(2+)-calmodulin dependent protein kinase II (CCDPK II) activity in rat hippocampus and striatum.
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We investigated the effect of cholecystokinin octapeptide (CCK-8) on plasma PRL levels in freely moving male rats. Intravenous injection of CCK-8 did not affect basal plasma PRL levels in doses up to 5000 ng/rat; however, plasma PRL increased significantly after intracerebroventricular (icv) injection of the peptide at a dose of 40 ng/rat. Proglumide (0.2 mg/kg, iv) and benzotript (0.2 mg/kg, iv), specific CCK receptor antagonists, blocked the icv CCK-8-induced increase in plasma PRL levels. There was no apparent effect of icv CCK-8 on the enhancement of PRL release by haloperidol (0.2 mg/kg, iv), sulpiride (0.1 mg/kg, iv), domperidone (0.1 mg/kg, iv), or RO22-1319 (0.1 mg/kg, iv). However, the apomorphine-induced inhibition of PRL secretion was significantly antagonized by icv CCK-8. Furthermore, icv CCK-8 increased plasma PRL levels in rats depleted of dopamine by pretreatment with reserpine and alpha-methyl-p-tyrosine. Finally, the elevation in plasma PRL levels produced by icv CCK-8 was substantially antagonized by vasoactive intestinal polypeptide antiserum (1:3; 10 microliter/rat, icv). These results suggest that CCK-8 increases plasma PRL through an interaction with a central CCK receptor, which stimulates the activity of vasoactive intestinal polypeptide, a putative PRL-releasing factor.
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Comparison of the TSH and PRL responses to dopamine antagonism with domperidone (10 mg i.v.) in patients with hyperprolactinaemia due to macroprolactinaemia or microprolactinomas.
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The review describes gastrointestinal receptors which are of therapeutic interest for the treatment of motility disorders. It updates the present knowledge on muscarinic, adrenergic, dopamine, opioid and dihydropyridine receptors, their subtypes, cellular sites and functional role as drug targets. On the basis of this pharmacological receptor concept, drugs like bethanechol, clonidine, lidamidine, metoclopramide, domperidone, cisapride, loperamide and nifedipine are evaluated in proven and potential indications. In view of the very complex regulation of motility, our understanding of receptors is still fragmentary and our tools to treat motility disorders do not fulfil all therapeutic requirements. This review tries to point out the areas of particular need for further basic research and the prospects of further drug development.
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Dopamine is reported to be a coronary vasodilator; however, the exact mechanism of dopamine action in the coronary circulation remains unclear. In this study, we hypothesized that dopamine-induced activation of coronary ATP-sensitive potassium (KATP) channels may be associated with coronary vasodilation. We therefore investigated the direct effects of dopamine on coronary KATP-channel activity.
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Domperidone (3 x 20 mg daily) was compared with ondansetron (3 x 8 mg daily) in a randomized double-bind placebo-controlled study. Out of 65 consecutive patients who received a first course of either cyclophosphamide and cisplatin for advanced stage ovarian cancer or cyclophosphamide, doxorubicin and 5-fluoro-uracil for metastatic breast carcinoma, 60 patients were eligible for entering the study. According to data from the literature these chemotherapeutic regimens with induce DN/V to a comparable degree. The patients were questioned daily from day 2 through day 5 by the same investigator and the severity of nausea or vomiting was scored on a numerical scale.
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All available medical reference systems were screened for the range of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies (EFNS) resulting in level A, B, or C recommendations and good practice points.
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The TSH and PRL responses to administration of the two dopamine (DA) receptor antagonists sulpiride and domperidone, were studied in fifteen normoprolactinaemic subjects, twenty-two post-partum women and sixteen subjects with presumptive evidence of (six subjects) or surgically confirmed (ten subjects) prolactinomas. Sulpiride (100 mg i.m.) or domperidone (10 mg i.v.) elicited a slight increase in basal TSH levels in both normoprolactinaemic and post-partum women, but induced a clear-cut TSH rise in subjects with a tumour. Conversely, sulpiride and domperidone strikingly stimulated PRL secretion in normoprolactinaemic and post-partum women, but only slightly enhanced base-line PRL levels in women with prolactinomas. The reason for the reciprocal pattern of TSH and PRL responsiveness to DA receptor blockade of post-partum women and subjects with prolactinomas is presently obscure. Since baseline PRL levels in the two hyperprolactinaemic states overlapped widely, it would appear that hyperprolactinaemia per se is not responsible for such behaviour.
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The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE were searched from 1966 through 2002. Additional strategies for identifying trials included searching the reference lists of review articles and included studies and searching books related to headache.
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Domperidone is a prokinetic agent widely prescribed in adults and children with gastrointestinal disorders. Recently several Regulatory Agencies published safety information on the risk of long QT syndrome associated with the use of domperidone. We conducted a literature review using PubMed (1966 - Jan 2010) with the aim to locate articles on ventricular arrhytmias, Sudden Cardiac Death (SCD), long QT syndrome and Torsade de Pointes (TdP) following domperidone administration. Twenty-two papers were included in the review: three studies in vitro models, one animal study, five case reports/series, twelve clinical studies and one editorial. In vitro studies demonstrated cardiac electrophysiological effects of domperidone on the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)) through the blockade of channels encoded by the Human Ether-a-go-go Related Gene (HERG). A total of fourteen cases of cardiotoxicity following intravenous (12 cases) or oral (2 cases) domperidone administration from case reports/series were identified. A case - control study, performed on a general practice observational database reported an OR: 3.8 (95% CI: 1.5-9.7) for SCD after domperidone exposure. Prescribers and other healthcare professionals should take into account the risk of QT syndrome in domperidone users and avoid administering domperidone in patients concomitantly taking strong CYP3A4 inhibitors or other QT prolonging drugs.
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A healthy, term male infant was weaned at 10 days postpartum because of his mother's illness. The baby was breastfed by his mother's sister, but mostly he was fed with his aunt's expressed milk and with formula by bottle. At 9 weeks postpartum relactation began. Techniques used were a supplemental nursing support system device; frequent suckle at the breast, supplemented by formula given by bottle; breast pumping; domperidone; and support from an International Board Certified Lactation Consultant and family. Problems that appeared during relactation were that at 12 postpartum weeks the baby refused the supplemental nursing system device, and at 12 weeks and 3 days he refused the breast; after 3 weeks of relactation, the milk supply was still low, needing supplementation; and in the first week of exclusive breastfeeding, the baby stopped growing, then he gained weight slowly, and his gain fell down to the 15(th) percentile. Solutions and interventions used to solve the problems were usage of an artificial nipple during breast strike for 3 days and cessation of supplementary formula and frequent suckling at the breast. Four days after relactation started, colostrum appeared (for 2 weeks), and within 1 month from the beginning of relactation the baby was fully breastfed. He was exclusively breastfed until 7 months, and he was continually breastfed until 2 years. His growth was good and was around the 50th percentile on the weight/length curve. Thus relactation is possible at 9 weeks postpartum, if the mother's motivation to breastfeed is strong. The best technique to increase milk supply is frequent, short breastfeedings.
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Repeated injections of amphetamine causes animals to become sensitized and supersensitive to DA. Previous work showed that the striata from such sensitized rats revealed a 3.5-fold increase in the density of D2(High) DA receptors, as measured by the guanine-nucleotide-sensitive component of [(3)H]raclopride binding. The present study was done to confirm these earlier findings by different methods and different ligands. The striata from amphetamine-sensitized rats showed an increase of 2.2-fold in the density of guanine-nucleotide-sensitive D2 receptors labeled by saturation experiments with [(3)H](+)PHNO. The proportion of D2(High) receptors was also found to increase 2.5-fold using the method of competition between DA and [(3)H]domperidone. The overall 2.2-3.5-fold increase of DA D2(High) receptors may explain why amphetamine-sensitized animals are much more sensitive to DA agonists, even though the total density of D2 receptors may apparently be unchanged or even decreased.