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At least 19 recordsLinked to original sources

PubMed1985

Comparison of ranitidine, domperidone maleate and ranitidine + domperidone maleate in the short-term treatment of reflux oesophagitis.

In the treatment of reflux oesophagitis, either drugs preventing regurgitation of gastric juice in the lower oesophagus or pharmacological agents increasing the pH of the refluxing material are employed. In the present study 45 outpatients with reflux oesophagitis were randomly treated with either ranitidine (150 mg b.i.d.) or domperidone maleate (20 mg t.i.d.) or both drugs for six weeks. Before and after treatment the severity of dyspeptic symptoms and the grade of endoscopic and histological changes were assessed. The three therapeutic regimens were significantly and equally effective in inducing symptomatic relief and promoting endoscopic and histological disappearance or improvement of oesophagitis. The combined use of ranitidine and domperidone maleate failed to show any additional benefit compared with treatment with either drug alone.

Clinical Trials as Topic↗

PubMed1979

Prevention of postoperative nausea and vomiting by domperidone: A double-blind randomized study using domperidone, metoclopramide and a placebo.

One hundred and ninety-five female patients of child-bearing age were assessed for postoperative vomiting in a double-blind trial using domperidone, metoclopramide and placebo. Compared with placebo, both drugs were found to reduce vomiting in approximately half the patients who had undergone caesarean section. However, in the group of non-obstetric patients, no statistically significant difference as regards vomiting was shown.

Adult↗

PubMed1979

[Effects of domperidone on gastrointestinal and gallbladder motility and gastric emptying (author's transl)].

Effects of domperidone on gastric emptying and gastric, duodenal and gallbladder motility were investigated. Intravenous injection of domperidone 2 mg/kg produced an acceleration of gastric motility without increase in the tone while a marked increase in the amplitude of peristaltic waves with a slight decrease in frequency was observed. Domperidone also produced an acceleration of duodenal and gallbladder motility. Domperidone produced an acceleration of transit of stomach contents in some cases, while in others gastric emptying was inhibited. This difference of the effect may be due to the previous tone of the pylorus. The excitatory action of domperidone on gastrointestinal motility was suppressed to some degree after cervical vagotomy or vagus cooling and markedly inhibited by atropine. Tetrodotoxin reduced the excitatory effect of domperidone but did not abolish. Therefore, it is presumed that domperidone stimulates, at least in part, the gastrointestinal muscle itself as well as cholinergic neurons in the gastrointestinal wall or cholinergic receptors of the gastrointestinal muscle and that domperidone may also have a central nervous system stimulant action. On the other hand, domperidone appears to act directly on the gallbladder muscle.

Action Potentials↗

PubMed1986

Effect of domperidone on the release of insulin after intravenous glucose load in man.

To determine whether the blockade of the dopaminergic system is capable of modifying glucose-induced insulin release in man, the responses of insulin to an iv glucose load were measured at various domperidone infusion rates. The infusion of 5 micrograms/kg/min of domperidone increased significantly plasma insulin levels during the acute phase of glucose-induced insulin release and lowered plasma glucose values at 50 and 60 min; the k of glucose disappearance improved significantly. At lower domperidone infusion rates the acute increment of insulin after glucose load was indistinguishable from the response observed at 5 micrograms/kg/min until 0.5 microgram/kg/min, while similar responses in control and experimental tests were observed at 0.25 microgram/kg/min. A group of subjects was submitted to an arginine load in order to establish whether the effect observed with domperidone was specific for the glucose-induced insulin release; but, this time, we did not observe any significant effect during the domperidone-induced dopaminergic blockade. Furthermore, we also measured the plasma prolactin levels, to see whether the specific and well known effect of domperidone on prolactin release matches with the effect on beta-cell function. As far as prolactin is concerned, we observed a dose response effect of domperidone infusion, with a detectable elevation of prolactin at infusion rate of 0.25 microgram/kg/min. Since domperidone is a specific antagonist of dopamine D2-receptors, we propose that dopamine might exert a specific inhibiting effect on glucose-induced insulin release through this class of dopamine receptors.

Adult↗

PubMed1991

Selective depletion of dopamine in the goldfish pituitary caused by domperidone.

The effects of the dopamine type-2 receptor (D-2) antagonist domperidone on pituitary and brain amine concentrations and serum gonadotropin levels in the goldfish were investigated. Domperidone caused a long-lasting, dose-dependent depletion of dopamine in the goldfish pituitary. Pituitary concentrations of 5-hydroxytryptamine (5HT) were unaffected by domperidone treatment. Concentrations of noradenaline, dopamine, and 5HT in the hypothalamus and telencephalon were also unaffected by domperidone treatment. In contrast to the goldfish, dopamine levels in both mouse pituitary and hypothalamus were unaffected by domperidone treatment. The depletion of dopamine was observed in both sexually regressed and recrudescent, male and female fish, but elevation of serum gonadotropin levels in response to domperidone treatment occurred only in sexually recrudescent fish. Treatment of sexually recrudescent fish with the D-2 antagonists pimozide, (-)-sulpiride and eticlopride and the dopamine type-1 (D-1) antagonists SKF 83566 and SCH 23390 failed to elicit a depletion of pituitary dopamine or elevation of serum gonadotropin. Treatment of sexually recrudescent fish with domperidone, alpha-methyl-p-tyrosine or carbidopa elicited comparable depletions of pituitary dopamine and elevations of serum gonadotropin. The results suggest that in addition to D-2 receptor antagonist activity, domperidone has some other neuropharmacological action on dopaminergic neurones in the goldfish pituitary.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMedDate not supplied

Pharmacokinetics and dose proportionality of domperidone in healthy volunteers.

Domperidone is a potent gastrokinetic agent and antinauseant currently undergoing clinical trials in the United States. The bioequivalence of 20 mg of domperidone given as free-base tablets and maleate salt tablets, and the bioavailability of base and maleate tablets relative to a solution, were studied in 21 fasting men using a crossover design. Plasma samples collected for up to 48 hours were analyzed for domperidone levels, using a sensitive and specific radioimmunoassay (RIA). The absorption of domperidone was very rapid, with mean peak plasma concentration (Cmax) values of 18.8, 15.0, and 20.7 ng/mL attained at 0.9, 1.2, and 0.6 hours after the administration of base tablet, maleate tablet, and solution, respectively. The mean elimination half-life (t1/2) ranged from 12.6 to 16.0 hours. The mean oral clearance (CL/F) after the solution dose was 4,735 +/- 2,017 mL/min and the mean apparent volume of distribution (Vd/F) was 6,272 +/- 5,100 L, indicating an extensive distribution of domperidone in the body. The area under the plasma concentration-time curve (AUC) data demonstrated bioequivalence of base and maleate tablets. The relative bioavailability for base tablet and maleate tablet was 107 +/- 50% and 116 +/- 47%, respectively, of that of the solution. Dose proportionality of domperidone was also studied in 12 subjects at solution doses of 10, 20, and 40 mg. Linear correlations between the dose and Cmax and AUC values were observed. Mean CL/F remained relatively constant after doses of 10, 20, and 40 mg (5,255 +/- 3,159, 4,842 +/- 1,774, and 4,380 +/- 1,289 mL/min, respectively), indicating linear pharmacokinetics of domperidone over the dose range studied.

Adult↗

PubMed1988

Domperidone, a DA2-specific dopamine antagonist, has no effect on the renal or haemodynamic response to atrial natriuretic peptide in man.

1. Animal experiments have suggested that the renal effects of atrial natriuretic peptide (ANP) are dependent on dopaminergic activation, predominantly of the DA1-receptor. In man, there is evidence of dependence on the DA2-receptor for the natriuresis produced by central blood volume expansion. 2. Six normal volunteers underwent infusions of alpha-human ANP preceded by domperidone (a DA2-antagonist) or placebo. Eight volunteers underwent a 3 h period of 10 degrees head-down tilt also preceded by domperidone or placebo. 3. Both the ANP infusion and head-down tilt produced a significant diuresis and natriuresis, neither of which was antagonized by the presence of domperidone. 4. The ANP infusion significantly reduced diastolic blood pressure and produced significant increases in the Doppler-measured aortic blood velocity variables of peak velocity and maximal acceleration. Domperidone had an independent effect of increasing blood pressure but did not appear to have a specific interaction with the haemodynamic effects of ANP. 5. Head-down tilt reduced mean arterial pressure and heart rate and increased maximal acceleration. Again, an independent effect of domperidone was seen on blood pressure. Heart rate and maximal acceleration showed similar changes in the presence of domperidone. 6. Domperidone does not antagonize the renal or haemodynamic effects of ANP and if dopaminergic activation is necessary for the renal action of ANP it is unlikely to be mediated by the DA2-receptor.

Atrial Natriuretic Factor↗

PubMed1987

TSH and PRL responses to domperidone and TRH in men with insulin-dependent diabetes mellitus of different duration.

The effect of domperidone, a specific blocker of dopamine receptors, on serum TSH and PRL levels was evaluated in 16 euthyroid men affected by insulin-dependent diabetes mellitus (IDDM) of different duration and in 7 age-matched normal controls. Diabetics were divided into 2 groups of 8 men according to the duration of their disease (group I: 1-9 years; group II: 11-18 years). Both groups had normal basal levels of TSH and PRL. Responses of these hormones to domperidone were similar in normal controls and in group I diabetics, whereas they were significantly reduced in patients of group II. When all 16 diabetics were studied together, a significant negative correlation was found between mean maximal peaks of TSH and PRL responses to domperidone and duration of diabetes. In order to evaluate whether the reduced effect of domperidone in diabetics was due to alterations of the dopaminergic control of TSH and PRL secretion, the domperidone test was repeated in 6 normal controls and in 6 diabetics of group II after infusion of dopamine (4 micrograms/kg/min for 2 h). Dopamine infusion induced parallel decreases in TSH and PRL concentrations, without modifying hormonal secretory patterns in response to domperidone. These data suggested that the reduced TSH and PRL responses to domperidone in diabetics were not due to alterations of the dopaminergic control of pituitary function but to a defect at the pituitary level. To test this hypothesis, TSH and PRL responses to TRH were evaluated in group I and group II diabetics and in normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

[3H]domperidone binding to the kidney inner medullary collecting duct dopamine-2K (DA2K) receptor.

Previous studies by our laboratory have indicated that inner medullary collecting ducts (IMCDs) express a novel dopamine (DA) receptor, designated DA2K, that is linked to stimulation of prostaglandin E2 production. This receptor has a distinct pharmacological profile and is similar in size, but not homologous to, the brain D2 receptor. Because the DA2-selective antagonist domperidone blocks DA-mediated stimulation of prostaglandin E2 production in IMCD cells, we utilized [3H]domperidone to study the binding characteristics of the DA2K receptor in IMCD cells. [3H]Domperidone binding was saturable and best fit to a single high density site (KD, 57.6 +/- 10.5 nM; Bmax, 14.9 +/- 2.7 pmol/mg protein). The specificity of [3H]domperidone binding in IMCD cells was verified by competition analysis with a variety of dopaminergic and nondopaminergic agents. Dopaminergic drugs were less potent competitors for [3H]domperidone binding in IMCD cells than previously reported for brain DA receptors, but the rank order was consistent with the labeling of a DA receptor [antagonists: domperidone greater than spiperone greater than haloperidol greater than Sch 23390 much greater than (-)-sulpiride; agonists: norapomorphine greater than fenoldopam much greater than dopamine = quinpirole], and was better correlated with the pharmacological profile for the brain D2 receptor than the brain D3 receptor. In addition, quinpirole, the most D3-selective ligand currently available, did not compete for [3H]domperidone binding in IMCD cells. These results add further support to the existence of a novel high density DA receptor, DA2K, expressed in IMCD cells.

Animals↗

PubMed1988

Effect of domperidone on the contractility of isolated guinea-pig atria.

This study was undertaken to investigate whether or not dopamine receptors are responsible for the cardiac action of domperidone and to gain a better understanding of the mechanism of the cardiac effects of this compound. In isolated electrically driven guinea-pig atria, domperidone (0.1-30 microM) produced a negative inotropic effect (-56.7 +/- 4.9% at 30 microM) and at a concentration of 0.1 microM significantly decreased the positive inotropic response to histamine (0.5-271 microM). In spontaneously beating guinea-pig atria, domperidone failed to modify the chronotropic responses elicited by dopamine and noradrenaline. In the isolated guinea-pig ileum, domperidone alone did not produce any effect, but produced a right-ward displacement of the contractile dose-response curve to histamine. At concentrations of 0.01, 0.1 and 1 microM, domperidone also depressed the maximum response to histamine. The results obtained suggest that the negative inotropic effect of domperidone is not due to dopamine or adrenergic receptor antagonism. This cardiac effect of domperidone can be partially explained by its influence on the effects of histamine acting on H1-receptors, although other mechanisms may be involved.

Animals↗

PubMed1978

Cytostatic-associated vomiting effectively inhibited by domperidone (R 33 812).

The effect of domperidone on vomiting due to cytostatic treatment was studied during a double-blind trial involving 41 patients. One group received the sequence domperidone-placebo and the other the reverse sequence during two consecutive courses of cytostatic therapy (chlormethine alone or in combination with other cytostatics). Domperidone 2 mg/ml or the placebo was injected IV 1 h before the start of the cytostatic treatment. A similar injection was given 4 h later. Presence, duration, and incidence of nausea and vomiting before, during, and after the peak period (period from the second up to and including the sixth hour after cytostatic injection) were measured. With respect to vomiting, domperidone was significantly superior to placebo concerning duration and effect before and after the peak period in both sequences. There was no difference during the peak period. With respect to nausea, domperidone was superior to placebo concerning duration and effect during the peak period in the placebo-domperidone sequence. No difference was observed in the reverse order. A significant superiority of domperidone was noted before the peak period.

Adult↗

PubMed1979

Effect of domperidone on gastric emptying and secretion.

Domperidone (5 mg i.v.) was given singly or together with apomorphine (0.25 mg i.v.) to healthy volunteers. The gastric emptying rate of a test meal of 750 ml of water was then measured using a dye dilution and double sampling technique. The effect of domperidone on gastric secretion was evaluated in patients with duodenal ulcer who received domperidone (5 mg i.v.) prior to continuous aspiration of the stomach contents for 120 minutes. Domperidone markedly increased the rate of emptying of the test meal. Following apomorphine the gastric emptying rate decreased and domperidone antagonized this slowing effect. The composition of gastric juice was not affected by an intravenous dose of domperidone. Domperidone appears to modulate gastric contractile activity without affecting gastric secretion.

Antiemetics↗

PubMed1987

Microwave facilitation of domperidone antagonism of apomorphine-induced stereotypic climbing in mice.

The dopaminergic agonist apomorphine produced dose-dependent stereotypic climbing behavior in mice housed in cages with vertical bars. This drug effect was competitively inhibited by systemic pretreatment with the centrally acting dopaminergic antagonist haloperidol but not by microwave irradiation (2.45 GHz, 20 mW/cm2, CW, 10 min) nor by systemic pretreatment with domperidone, a dopaminergic antagonist that only poorly penetrates the blood-brain barrier (BBB). Yet when mice were systemically pretreated with domperidone and then subjected to microwave irradiation (as above), the apomorphine effect was significantly reduced. Microwave irradiation also facilitated antagonism of the apomorphine effect by low and otherwise ineffective systemic pretreatment doses of haloperidol. Apomorphine-induced stereotypic climbing behavior was also reduced by domperidone administered intracerebrally, which bypassed the BBB. Exposure of intracerebral domperidone-pretreated animals to microwave irradiation failed to increase the degree of antagonism. These findings indicate that microwave irradiation can facilitate central effects of domperidone, a drug which acts mainly in the periphery. One possible explanation for these findings is that microwave irradiation alters the permeability of the BBB and increases the entry of domperidone to central sites of action.

Animals↗

PubMed1988

Effects of domperidone in patients with chronic unexplained upper gastrointestinal symptoms: a double-blind, placebo-controlled study.

The effects of domperidone, a peripherally acting dopamine antagonist, were compared with those of placebo in a double-blind randomized study in 16 patients with idiopathic gastric stasis, chronic symptoms of "nonulcer dyspepsia" (including nausea, vomiting, and abdominal pain), and altered gastroduodenal motility. Patients received either domperidone or placebo orally (20 mg before meals and at bedtime) for six weeks. Symptoms were assessed by daily diaries kept by the patients for two weeks while receiving no medication for their gastrointestinal complaints (baseline), and throughout the six-week treatment phase. Studies of gastric emptying of a radiolabeled solid-phase meal were performed at baseline and six weeks after treatment. All patients had delayed gastric emptying at baseline, defined as a half-emptying time of more than mean + 1 SD (from studies of normal controls). An 18- to 24-hr recording of gastroduodenal motor function during fasting was also performed at baseline and after six weeks of either domperidone or placebo treatment. After six weeks of treatment, the symptom scores significantly improved in the domperidone group (P less than 0.05), but not in the placebo group. Gastroduodenal motor activity was unchanged from baseline recordings after six weeks. Solid-phase gastric emptying also showed no improvement in either the domperidone or placebo group of patients. Although domperidone therapy had no significant effect on motility, it appears to be an effective drug for the treatment of the symptoms of nonulcer dyspepsia.

Adult↗

PubMed1987

Effects of domperidone and thyrotropin-releasing hormone on secretion of luteinizing hormone and prolactin during the luteal phase and following induction of luteal regression in sheep.

Effects of domperidone, a peripheral dopamine receptor antagonist, on secretion of LH and prolactin were studied during the luteal phase and following administration of PGF2 alpha. Since hyperprolactinemia has been reported to inhibit secretion of LH in ewes, effects of thyrotropin-releasing hormone (TRH) also were examined. Ewes 8-10 days post-estrus were assigned to be treated with: 1) vehicle (n = 5); 2) 0.3 mg domperidone (n = 6); 3) 1.0 mg domperidone (n = 6); 4) 3 micrograms TRH (n = 6); or 5) 10 micrograms TRH (n = 6) every 4 hours for 60 hr. Luteal regression was induced with PGF2 alpha at 12 hr after initiation of treatments. During the luteal phase, pulses of LH were more frequent (P less than .05) and the amplitudes of these were higher (P less than .05) in ewes treated with domperidone or TRH than in control ewes. These changes in LH occurred even though each treatment elevated markedly concentrations of prolactin in plasma. After induction of luteal regression, mean of LH and frequency of LH discharges were similar in all groups. However, in ewes treated with the 1.0 mg/4 hr dose of domperidone the pulse amplitude was greater than in the other groups (2.3 vs 1.1 ng/ml). Dose-response relationships and the magnitude of the prolactin release following domperidone or TRH varied with time. Treatments did not affect the timing of the LH surge or the increase in progesterone associated with the subsequent cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Interactions between domperidone and ropinirole, a novel dopamine D2-receptor agonist.

1. Ropinirole, SK&F 101468 has been characterized preclinically as a specific dopamine D2-receptor agonist. Nine male healthy subjects were investigated for the effects on supine and erect heart rate and blood pressure, catecholamines and prolactin, of a single dose of 800 micrograms ropinirole preceded by a single dose of 20 mg domperidone or domperidone-placebo, and those of a single dose of domperidone followed by ropinirole-placebo. 2. Single doses of 800 micrograms ropinirole did not cause clinically significant changes in supine resting heart rate and blood pressure. However, they caused postural faintness on 3 min immobile upright standing on 10/26 occasions. 3. Pretreatment with 20 mg domperidone 1 h before administration of ropinirole prevented the postural symptoms in all but one subject. It did not alter ropinirole's plasma pharmacokinetics. 4. Ropinirole did not alter supine or standing catecholamine concentrations. 5. Domperidone increased the plasma concentrations of prolactin whereas ropinirole administered alone reduced them. A single dose of 800 micrograms ropinirole did not attenuate the prolactin increase induced by a single dose of 20 mg domperidone administered 1 h earlier.

Adult↗

PubMed1985

Effect of domperidone on gastro-oesophageal function in normal human subjects.

The aim of the study was to investigate gastro-oesophageal function in normal volunteers after oral administration of domperidone as a single dose (20 mg). The study was designed as a double-blind cross-over investigation. Ten healthy men (aged 27-50 years; median, 30) joined the study. Oesophageal function tests were performed, starting 1.5 h after intake of domperidone or placebo. Gastro-oesophageal sphincter pressure was measured with a perfused catheter system and a continuous pull-through technique. No changes in sphincter pressure were found. Peristaltic pressure amplitude in the body of the oesophagus and the duration and velocity of peristalsis were measured after wet swallows (bolus 5 ml of water). No changes were found. Intragastric pH did not change significantly after domperidone. No effect of domperidone on the results of a standard acid-clearing test could be found. Plasma concentrations of domperidone did not correlate with any of the other variables. In conclusion, domperidone given orally in a dose that has been shown to accelerate gastric emptying does not influence gastro-oesophageal sphincter pressure or peristaltic activity in the normal oesophagus.

Adult↗

PubMed1985

Evaluation of the combined effects of atropine and domperidone on the lower oesophageal sphincter.

The effects of sequential administration of both domperidone followed by atropine, and atropine followed by domperidone were examined on the lower oesophageal sphincter of 10 healthy volunteers. Domperidone, 10 mg, increased lower oesophageal sphincter pressure (LOSP) within 10 min of injection. Atropine, 0.6 mg given at the time of peak effect of domperidone, subsequently decreased LOSP. However, frequent measurement of LOSP during the succeeding 40 min demonstrated that LOSP did not decrease significantly below control levels during this drug sequence. When the drugs were administered in the reverse sequence, atropine, 0.6 mg, decreased LOSP within 5 min of injection and subsequent administration of domperidone, at the time of peak effect of the atropine, resulted in a gradual increase in LOSP. However, control values were not approached until 30 min had elapsed after the administration of the domperidone.

Adult↗