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Nausea and vomiting are common symptoms of migraine, which can be controlled with a variety of anti-emetics including phenothiazines and antihistamines. Metoclopramide and domperidone have an additional prokinetic effect which may be important in migraine to overcome gastric stasis and enhance absorption of oral medication.
Domperidone, a "hidden" neuroleptic, is used for symptomatic treatment of gastroesophageal reflux disease, despite its uncertain efficacy. The intravenous form was withdrawn from the market in the 1980s following deaths due to cardiac arrhythmias. QT prolongation leading to cardiac arrhythmias, including life-threatening torsades de pointes, has also been attributed to oral domperidone. In 2010, two case-control studies, one Canadian and one Dutch, showed that patients who died suddenly or had severe ventricular arrhythmias were statistically significantly more likely than controls to have been exposed to domperidone. In practice, given its uncertain efficacy and a disproportionate risk of sudden death and severe ventricular arrhythmia, domperidone should not be used.
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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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Changes in mean aortic pressure and heart rate, induced by treatment with 150 micrograms.kg-1 bromocriptine intravenously, were measured in conscious or anaesthetised normal or adrenalectomised rats submitted to various pretreatments.
Apomorphine exerts pro-erectile effects by acting on neurons in the paraventricular nucleus of the hypothalamus. In spinal cord injured rats we assessed whether apomorphine also directly activates the spinal autonomic and somatic neurons controlling penile erection
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Before the black box warning, 69.8% of patients received metoclopramide for gastroparesis, compared with 23.7% after the warning. Gastroenterologists prescribed domperidone more often after than before the warning. Metoclopramide prescriptions decreased after 2008. Adverse event reporting increased after the warning. Only 3.6% of all FAERS reports but 70% of TD reports were filed by lawyers, suggesting a distortion in signal. Forty-seven legal opinions were identified, 33 from 2009-2010.
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Levels of estradiol-17 beta (E2), testosterone (T), 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (DHP), and 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S) were measured by radioimmunoassay (RIA) in blood plasma of striped bass undergoing final oocyte maturation (FOM). Females were captured just prior to, or in the early stages of, FOM and induced to complete maturation and ovulation with injected human chorionic gonadotropin, synthetic salmon gonadotropin-releasing hormone analogue (sGnRHa; [D-Arg6-Pro9 NEt]-sGnRH), sGnRHa plus the dopamine receptor antagonist, domperidone (DOM), or OVAPRIM, a commercial preparation of sGnRHa + DOM. Their plasma levels of immunoreactive DHP and 20 beta-S were significantly greater at ovulation relative to the time of hormone injection, whereas the plasma levels of E2 and T were greatest at injection and decreased by ovulation and 24 hr thereafter. Plasma levels of 20 beta-S, but not DHP, were sustained at high levels after ovulation. Fish injected only with DOM did not undergo FOM, its associated changes in plasma steroid levels, or ovulation. In females captured at various natural stages of FOM, plasma levels of 20 beta-S and DHP were low during germinal vesicle migration (GVM), peaked coincident with germinal vesicle breakdown, and then decreased near the time of ovulation. Plasma levels of E2 and T were greatest during GVM and decreased as DHP and 20 beta-S levels increased. Analyses of conjugated versus free plasma steroids showed 64-79% of the various hormones to be in the free fraction. RIA of plasma fractionated by reversed-phase HPLC showed that half of the 20 beta-S immunoreactivity coeluted with 5 beta-pregnan-3 alpha,17,20 beta,21-tetrol, a putative 20 beta-S metabolite with 99.7% cross-reactivity in the 20 beta-S RIA. These results indicate that striped bass follow the typical profile of changing plasma steroid levels seen in other teleosts during FOM, with a clear shift from C18 and C19 steroids to C21 steroids. They suggest that both DHP and 20 beta-S, both potent inducers of striped bass FOM in vitro, may play a role in regulating FOM in this species.
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The effect of domperidone (2 mg kg-1) on the pharmacokinetics of a single oral dose of theophylline (25 mg kg-1) was studied in the rat. Theophylline concentrations were measured serially for 12 h using an HPLC technique. Domperidone did not have any significant effect on any of the four parameters studied: peak plasma levels (Cpmax), the time these were attained (tmax), elimination half-life (t1/2) and area under the plasma concentration-time curve (AUC). Our data preliminarily suggests that domperidone may be safely coadministered with theophylline but clearly further studies in patients or relevant animal models of gastric motility disturbances are needed to reliably rule out any potential interaction between these agents.
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No changes of pharmacokinetic parameters describing systemic exposure and renal elimination of rotigotine were observed when domperidone was administered concomitantly with rotigotine. The lack of pharmacokinetic interactions indicates that a dose adjustment of rotigotine transdermal patch is not necessary with concomitant use of domperidone.
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The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous treatment with the non specific dopamine receptor antagonist, haloperidol (9 mg/kg IP), or the D2 antagonist domperidone (2 mg/kg IP), but not by the D1 antagonist SCH 23390 (1 mg/kg IP). The apomorphine-induced decrease in adrenal catecholamine concentration was suppressed by denervation of the adrenal medulla, i.e. unilateral section of splanchnic fibers performed 5 days before. These results show that, under our experimental conditions, the effect of apomorphine is due to the activation of D2 dopamine receptors probably located on splanchnic nerve endings and suggest the existence of a peripheral D2 dopaminergic system which modulates adrenal medullary catecholamine content.
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A double-blind crossover study was conducted of two gastric prokinetic drugs in 23 patients with gastroesophageal reflux. Patients were divided into two groups on the basis of a dual-isotope mixed-meal study of their gastric emptying (GE). Group I had normal GE and group II delayed GE. Nine gastrointestinal symptoms were assessed for frequency and severity before treatment. The trial had three 1-month treatment periods using metoclopramide 10 mg q.i.d., domperidone 20 mg q.i.d., or placebo on a random basis. Symptoms were reassessed at the end of each month. Taken as a whole, the group showed a significant symptomatic response in all three treatment periods (p less than 0.0001), but patients with delayed or normal GE did not differ significantly in their symptomatic response. Eleven patients complained of side effects with metoclopramide and three stopped therapy before the 1-month course was completed. Two patients described side effects with domperidone, including one woman with galactorrhea after 36 h of treatment. Three patients on placebo also complained of important side effects. We conclude that a significant placebo effect is present in the treatment of gastroesophageal reflux. No significant difference was demonstrated in symptomatic improvement between placebo, domperidone, and metoclopramide in this study.
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Fluctuations in motor performances are the major problem in the longterm management of Parkinson's disease. In this study the clinical effects of L-dopa intravenous infusion were evaluated in 18 parkinsonian patients with fluctuations. 14 out of these were given Lisuride intravenous infusion in a following study. Lisuride is a potent dopamine agonist and it is highly soluble in water. The results obtained with L-dopa were very good and we found a close correlation between oral and intravenous dosage. The dosage of L-dopa infusion ranged between 360-1,250 mg for 12 hours. Lisuride proved to be able to give prolonged mobile state in 8 patients out of 14. The other 6 patients showed a different response to the drug. The dosage used ranged between 0.6 and 2.4 mg per day. No severe side-effects were observed during both studies except for nausea and vomiting occurring during Lisuride infusion.
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Prolactin (Prl) and growth hormone (GH) responses to different pharmacologic probes acting at the central nervous system (CNS) or the anterior pituitary (AP) level were evaluated in patients with distinct neuro-endocrine disorders. Thirteen patients with Prl-secreting tumours (PST), 10 acromegalics (A) and 8 patients with hypothalamic lesions (HL), as assessed on clinical, radiological and surgical grounds, underwent on separate occasions acute testing with the opioid peptide FK 33-824 (0.5 mg iv), the indirect dopamine (DA) agonist nomifensine (NOM, 200 mg po), the DA receptor antagonist domperidone (DOM, 10 mg iv), TRH (200 microgram iv) and insulin (ITT, 0.10-0.15 IU/kg iv). All patients were evaluated pre-surgery and 4 of them also post-surgery. Prl and GH were evaluated by RIA at different time intervals following treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute gastroenteritis (AGE) is a common condition among children that is frequently accompanied by vomiting. Symptomatic control of vomiting is important as it improves patient's general condition and reduces the need for intravenous therapy and hospitalization. Antiemetic agents including ondansetron and domperidone are used to provide symptomatic relief but the existing studies do not provide enough evidence of better efficacy for one over another.
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Synthetic gastrin releasing peptide (GRP) injected intraventricularly (1 microgram/rat), but not intravenously, suppressed rat prolactin (PRL) release induced by a Met-enkephalin analog, FK33-824 (10 micrograms/100 g body wt., iv). GRP also blunted PRL release induced by a dopamine antagonist, domperidone (1 microgram/100 g body wt., iv). In contrast, GRP did not suppress elevated plasma PRL levels sustained by a large dose of domperidone (10 micrograms/100 g body wt., iv). GRP (10(-5) M) had no effect on PRL release from superfused pituitary cells in vitro. These results suggest that GRP inhibits PRL secretion in the rat by acting through the brain to stimulate the dopaminergic mechanism.
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Following treatment with dopamine (DA) receptor agonists, such as apomorphine, N-n-propyl-norapomorphine, lisuride and 3-(3-hydroxyphenyl)-N-n-propyl-piperidine (3-PPP) (50, 2.5, 400 and 5000 micrograms/kg, respectively), male rats attain ejaculation with receptive females sooner and after fewer penile intromissions than controls. Since doses of DA agonists needed to produce "premature ejaculation" are within the low dose range needed to stimulate DA autoreceptors, it is suggested that "premature ejaculation" in rats results from inhibition of DA neurotransmission. This hypothesis is supported by the finding that 6 hr after haloperidol (1 mg/kg), rats achieve ejaculation after fewer intromissions than normal.
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A comparative study between two dopaminergic antagonists: metoclopramide and domperidone, was undertaken in nineteen (19) hypertensive patients at the Vargas Hospital, Caracas. The patients were pretreated with labetalol, 800-1,200 mg/day, orally, over a period of one week, after which they were divided into two groups: group A, a total of eleven patients were intravenously infused with dopamine hydrochloride 0.5-3 micrograms/kg/min, before and after treatment with metoclopramide (10 mg, i.v. as a bolus); group B (n = 8), was pretreated with domperidone, 20 mg b.i.d., p.o. over a period of one week and intravenously infused with dopamine hydrochloride, 0.5-3 micrograms/kg/min. In group A, dopamine induced a decrease of blood pressure from 171.9 +/- 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97 mmHg (p < 0.001) without altering heart rate, and it increased plasma insulin levels from 8.29 +/- 0.70 microunits/ml to 12.09 +/- 1.83 microunits/ml (p < 0.01). Metoclopramide caused no changes of blood pressure or plasma insulin levels. However, hypotensive responses and plasma insulin rises due to dopamine were blocked by metoclopramide. In group B, domperidone also blocked dopamine-induced antihypertensive effect (from 170.0 +/- 9.23/102.8 +/- 3.80 to 160.2 +/- 9.84/95.5 +/- 2.50 mmHg) although it was less effective than metoclopramide. Domperidone also blocked dopamine-induced increase of plasma insulin levels from 9.65 +/- 4.50 microunits/ml to 11.78 microunits/ml. We conclude that a dopaminergic receptor may be involved in some cardiovascular responses and in modulating insulin secretion in man.
Endothelin-3 (ET-3) inhibited in a dose-dependent, significant fashion prolactin release from cultured anterior pituitary cells (ovariectomized female and intact male rat donors, ED50 = 5 X 10(-9) M). ET-3 in log doses ranging from 10(-11) to 10(-6) M did not alter significantly the release of luteinizing hormone, growth hormone or thyroid stimulating hormone. The inhibitory effect of ET-3 (rat, human) was specific for that molecule since ET-1 (porcine, human) was ineffective and was not due to an action on the dopamine receptor since the inhibitory action was still expressed in the presence of 100 nM domperidone. These data further suggest a role for neuropeptides of the posterior lobe in the control of lactotroph function.
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Overall, the group-analysis showed no statistical significant difference in QTc duration induced by domperidone. However, 2/45 (4.4%) infants had a prolonged QTc interval (> 460 msec) induced by domperidone. As a consequence, QTc measurement should be recommended in routine in infants when domperidone is started.
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Domperidone is often used to promote lactation among women who have difficulty breastfeeding.