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Gravid mares grazing endophyte-infested (E+) tall fescue exhibit increased gestation lengths, agalactia, foal and mare mortality, tough and thickened placentas, weak and dysmature foals, increased sweating during warm weather, reduced serum prolactin and progesterone, and increased serum estradiol-17 beta levels. Also, E+ tall fescue hay is less digestible than endophyte-free (E-) hay. Unlike many other species, horses consuming E+ tall fescue do not exhibit increased body temperature. Young horses consuming only E+ pasture do not gain as well as those consuming E- pasture. There is little difference in gain when the pasture is supplemented with enough concentrate to meet NRC requirements for growth. Neither selenium injections nor supplementing with corn at 50% of the NRC requirements for energy reduces the effects of toxic tall fescue on reproduction and lactation in gravid mares. It seems that the alkaloids of E+ tall fescue are serving as D2 dopamine receptor agonists. This activity would explain their prolactin-lowering effect. Domperidone, a dopamine receptor antagonist, is effective in preventing the signs of tall fescue toxicosis in horses without neuroleptic side effects.
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To observe the clinical efficacy and safety of Jinghua Weikang Capsule (JWC) on chronic gastritis (CG).
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Recent studies showed that a brief interruption of dopamine (DA) action markedly increased the thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) release. It is thus of interest to delineate whether the estrogen-induced afternoon PRL surge involves the same mechanism. Long-term ovariectomized rats pretreated with polyestradiol phosphate (PEP, 0.1 mg/rat s.c.) for 6 days were used in this study. They also received either p-chlorophenylalanine (PCPA, 250 mg/kg i.p.) or ketanserin (Ket, 10 mg/kg i.p.), two serotonergic drugs known to inhibit the estrogen-induced afternoon PRL surge. Then the animals were either treated with a DA antagonist, domperidone (Domp, 0.01 mg/rat i.v.), or vehicle at 16.00 h on the sampling day. Ten minutes later, the ones receiving Domp were injected with a DA agonist, 2-bromo-alpha-ergocryptine (CB154, 0.5 mg/rat i.v.), followed 50 min later by the administration of TRH (1 microgram/rat i.v.). Plasma samples taken through indwelling intraatrial catheters were assayed for PRL by radioimmunoassay. The estrogen-induced afternoon PRL surges were completely blocked in both PCPA- and Ket-treated animals. A significant PRL surge with similar amplitude, however, was induced by either Domp or TRH, although pretreatment with Domp did not cause any potentiating effect on the action of TRH. On the other hand, Domp induced only a small rise of PRL secretion and TRH was totally ineffective in rats untreated with PEP. It is concluded that both DA antagonism and TRH stimulation can induce significant PRL release in the afternoon of estrogen-treated, serotonin-blocked rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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Larrain A; Kapur VK; Gooley TA; Pope CE. Pharmacological treatment of obstructive sleep apnea with a combination of pseudoephedrine and domperidone.
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The induction of lactation is performed in ruminants by steroidogenic impregnation, followed by drugs intended to increase prolactin secretion. The aim of this study was to induce lactation in barren mares and to evaluate milk production. Five treated and 5 control mares were used in June and September in year 1, and 12 mares were used in year 2. Mares were administered a vaginal pessary (500 mg altrenogest and 50 mg estradiol benzoate) for 1 week. The 2nd week, another sponge with 100 mg estradiol benzoate was administered, together with 50 mg/100 kg body weight (BW) sulpiride in oil (IM q12h). All mares were milked by hand. Drug treatment was stopped after I L was obtained. Milk production and composition and plasma prolactin concentration were measured. In year 2, the same steroid treatment was applied, but mares received sulpiride (n = 6) or domperidone (1.1 mg/kg PO q12h) (n = 6). A milking machine and oxytocin injections 1 minute before the start of milking were used. In year 1, all treated mares started milking within 1-5 days after sulpiride treatment. Mean daily milk production was 0.88 +/- 0.52 L/500 kg BW. Milk immunoglobulin G (IgG) contents increased in all mares (IgG concentration range, 14-92 g/L). Plasma prolactin increased during sulpiride treatment (range. 27.7 +/- 2.9 to 43.7 +/- 6.7 ng/mL [before] to 289.0 +/- 7.8 ng/mL during treatment, P < .001). In year 2, results were similar to those in year 1, with peak IgG concentrations ranging from 4.2 to 106.7 g/L and a larger daily milk production (3.13 +/- 0.75 with sulpiride and 3.45 +/- 0.51 L/500 kg BW with domperidone). In conclusion, lactation can be induced in mares within 2 weeks, and some mares produce good-quality colostrum.
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Effects of fenoldopam, a selective DA1 dopamine receptor agonist, and dipropyl dopamine and propylphenethyl dopamine, preferential DA2 dopamine receptor agonists, on ganglion transmission were studied in pentobarbital-anesthetized, open-chest dogs. Tachycardia induced by electrical stimulation (supramaximal voltage, 0.5 ms duration, 1-2 Hz) of the preganglionic cardio-accelerator nerves was monitored as a measure of ganglionic transmission. Drugs were injected into the costocervical artery (i.a.) close to the arterial supply of the ganglion. Doses required to produce 30-40% inhibition of ganglionic transmission by the i.a. route were 2-8 micrograms for dipropyl dopamine, 4-16 micrograms for propylphenethyl dopamine, and 100 micrograms for fenoldopam. At these doses none of the agonists affected tachycardia induced by electrical stimulation of the postganglionic nerve. Domperidone (5 micrograms/kg i.v.), a selective DA2 dopamine receptor antagonist, markedly antagonized the effects of dipropyl dopamine and propylphenethyl dopamine, but had only minor (and statistically insignificant) effects on the inhibitory effect of fenoldopam. SCH 23390 (5 micrograms/kg i.v.), a selective and potent DA1 antagonist, failed to modify the effects of any of the agonists. In a separate series, infusion of fenoldopam, 20 micrograms/kg per min i.v. for 5-7 min, facilitated postganglionic nerve stimulation and blocked the inhibitory effect of UK 14,304, an alpha 2-adrenoceptor agonist, on the postganglionic nerve. These results confirm and support the presence of DA2 but do not support the presence of the prototypal DA1 dopamine receptor in the mammalian ganglia. Furthermore, the alpha 2-adrenoceptor blocking property of fenoldopam points to the complication of using i.v. administration for studying its ganglionic actions while monitoring the target tissue effects in response to preganglionic nerve stimulation.
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Many functional dyspepsia treatment trials have until recently suffered from important weaknesses in study design. A major problem has been the low number of studies that have used validated outcome measures. Fortunately, progress has been made in this area. The evidence for the efficacy of antacids, H2-receptor antagonists, omeprazole, domperidone, cisapride and anti-Helicobacter therapy is reviewed. Although several of these have shown benefit, it is unclear whether this may be a result of the inclusion of patients with unrecognized gastro-oesophageal reflux disease. The data on anti-Helicobacter therapy are conflicting.
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To study the effects of propylbutyldopamine (PBDA) on the inward rectifier potassium current (Ik1).
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To compare the therapeutic effects of acupuncture and Motilium on diabetic gastroparesis (DGP).
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Gastroparesis is an important clinical disorder characterised by delayed gastric emptying in the absence of mechanical outlet obstruction. Idiopathic, diabetes and postsurgical causes represent the most common aetiologies. The condition commonly manifests as upper gastrointestinal symptoms, including nausea, vomiting, postprandial fullness, early satiety, abdominal pain and bloating.
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In spontaneously hypertensive rats (SHRs) the dopaminergic D1-like renal vasodilator response is impaired. The renal vascular response to D2-like receptor stimulation in vivo is incompletely known. Therefore, renal hemodynamics were studied in conscious SHRs during continuous infusion of D2-like agonist N,N-Di-n-propyldopamine (DPDA) (10 microg/kg/min) with Wistar-Kyoto (WKY) rats as controls. As sodium status may affect dopaminergic responses, rats were studied during both low- and high-sodium diets. D2-like stimulation reduced mean arterial pressure and effective renal plasma flow and glomerular filtration rate (GFR) similarly in SHR and WKY rats. Renal vascular resistance increased significantly in both strains. The response to DPDA is modified by sodium status, with a more pronounced fall in blood pressure (in WKYs and SHRs) and GFR (in WKYs) during high-sodium conditions. The responses were blocked by co-infusion with D2 antagonist domperidone. Thus, D2-like renal vascular responses are normal in SHRs irrespective of sodium intake. The combination of a preserved D2-like renal vasoconstrictive and an impaired D1-like renal vasodilatory response may contribute to maintenance of hypertension in SHRs.
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The electrochemical response of an unmodified glassy carbon (GCE), poly-melamine/GCE and gold nanoparticle (AuNP)/poly-melamine/GCE is compared in the present protocol for the sensitive and selective determination of domperidone (DOM). The AuNPs were synthesized in the laboratory and characterized using UV-visible spectroscopy and Transmission Electron Microscopy (TEM). Melamine was electropolymerized onto the glassy carbon surface using cyclic voltammetry and was investigated using Field Emission Scanning Electron Microscopy (FE-SEM) and Electrochemical Impedance Spectroscopy (EIS). The AuNP/poly-melamine/GCE exhibited the best electrochemical response among the three electrodes for the electro-oxidation of DOM, that was inferred from the EIS, cyclic and square wave voltammetry. The modified sensor showed a sensitive, stable and linear response in the concentration range of 0.05-100µM with a detection limit of 6nM. The selectivity of the proposed sensor was assessed in the presence of high concentration of major interfering molecules as xanthine, hypoxanthine, and uric acid. The analytical application of the sensor for the quantification of DOM in pharmaceutical formulations and biological fluids as urine and serum was also investigated and the results demonstrated a recovery of >95% with R.S.D of <5%.
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In the irritable bowel syndrome gastrointestinal tract motility is disturbed from the esophagus to the colon, causing pain and altered function. When colonic motility is abnormal, the patient can experience either constipation or diarrhea in addition to abdominal pain and bloating. In constipated patients the postprandial colonic motility can increase normally after eating or the colon can remain motionless. Generally propagating contractions are absent in patients with constipation predominant irritable bowel syndrome. Propagating contractions are increased in frequency in patients with diarrhea, although the phasic contractions are decreased. Questionnaires discriminate between patients with structural disease such as ulcerative colitis and patients with functional disease, however they cannot differentiate between the different subgroups of patients with constipation predominant irritable bowel syndrome. Treatment strategies are beginning to focus on the underlying pathophysiologic abnormality.
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The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w). The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer) and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm(2) and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4). Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4) with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.
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Gastric emptying of the fed guinea-pig was measured using a non-invasive X-ray fluoroscopic technique to determine passage from the stomach of polystyrene-coated barium sulphate spheroids. Peripherally administered metoclopramide (0.1-10 mg/kg i.p.), clebopride (1-10 mg/kg i.p.), (-)-sulpiride (40 mg/kg i.p.), haloperidol (1 mg/kg i.p.) and domperidone (1-10 mg/kg i.p.) failed to modify gastric emptying. Stress inhibited emptying, and this was considered to explain the effects of eserine and high dose metoclopramide. Gastric emptying was decreased by peripherally administered atropine (0.5 mg/kg i.p.) and apomorphine (0.1-0.5 mg/kg s.c.); the apomorphine response was antagonised by pretreatment with haloperidol, domperidone, (-)-sulpiride, metoclopramide and clebopride but not by prazosin + propranolol. Gastric emptying was facilitated by intracerebroventricular (i.c.v.) administrations of metoclopramide and clebopride (40, 100 and 200 micrograms) but not by i.c.v. domperidone, haloperidol, fluphenazine or (-)-sulpiride (100, 200 micrograms) and was inhibited by i.c.v. apomorphine (100, 200 micrograms); the response to i.c.v. apomorphine was antagonised by i.c.v. pretreatments with haloperidol, domperidone, (-)-sulpiride, metoclopramide and clebopride (40-50 micrograms). Facilitation of emptying by i.c.v. metoclopramide was prevented by peripheral pretreatment with atropine (0.5 mg/kg i.p.). It is concluded that the actions of apomorphine and metoclopramide/clebopride to respectively inhibit and facilitate gastric emptying may be mediated, at least in part, via central mechanisms. Whilst apomorphine's action may be mediated via dopamine receptor mechanisms, metoclopramide and clebopride act at additional unspecified sites, metoclopramide's action being expressed via cholinergic mechanisms.
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The effects of diphenhydramine, domperidone, ondansetron, and diphenidol on motion- and apomorphine-induced pica (i.e., kaolin ingestion) in rats as the measure analogous to emesis in other species were examined. Diphenhydramine (10 and 20 mg/kg) and diphenidol (30 mg/kg) inhibited kaolin intake induced by 60-min double rotation, while domperidone and ondansetron did not. Kaolin intake induced by apomorphine (10 mg/kg) was inhibited by domperidone (2 mg/kg) and diphenidol (30 mg/kg), but not by diphenhydramine or ondansetron. These findings suggest that the emetic pathways through the inner ear (double rotation) and the chemoreceptor trigger zone (apomorphine) are pharmacologically independent and are mediated by histamine H1 receptors and dopamine D2 receptors, respectively. Diphenidol may inhibit a common locus of emesis.
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Administration of LY171555, a specific dopamine D2 receptor agonist, (10-1000 micrograms/kg i.v.) produced dose-related increases in mean arterial pressure in conscious Sprague-Dawley rats. Pretreatment with metoclopramide (5 mg/kg i.v.) abolished the pressor action of LY171555, whereas pretreatment with domperidone (2.5 mg/kg i.v.) and propranolol (10 mg/kg i.p.) did not affect the pressor action of LY171555. The vasopressor antagonist of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP (10 micrograms/kg i.v.) and phenoxybenzamine (1 mg/kg i.v.) partly blocked and hexamethonium (25 mg/kg i.v.) enhanced the pressor action of LY171555. After combined treatment with both d(CH2)5Tyr(Me)AVP and phenoxybenzamine, LY171555 induced a depressor response which was completely blocked by pretreatment with domperidone. LY171555 administration induced a rapid, short-acting depressor response followed by a pressor response in conscious adrenomedullectomized Sprague-Dawley rats which was smaller in magnitude than that seen in intact Sprague-Dawley rats. LY171555 administration increased plasma norepinephrine, epinephrine and AVP in conscious Sprague-Dawley rats. These results suggest that the pressor action of LY171555 in conscious rats is dependent on activation of sympathetic outflow and AVP release through the central D2 dopaminergic system and that the central pressor effects of LY171555 could mask a depressor effect of LY171555 at the peripheral D2 dopamine receptor.
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Dopamine (DA) and DA agonists have been shown to exert a protective role against the formation of duodenal ulcers. The effect of stimulation of DA receptors on the development of stress-induced gastric ulcers is currently unknown. Accordingly, we evaluated the effect of several DA agonists on the development of gastric ulcers induced by 3 h of cold + restraint stress (CRS) in rats. Apomorphine, d-amphetamine, methylphenidate, and threo-dl-p-hydroxymethylphenidate (an hydroxylated analog of methylphenidate), significantly reduced both the incidence and severity of CRS-induced gastric ulcers. The gastric cytoprotection afforded by these agents was dose-related, and completely antagonized by pretreatment with the peripherally acting DA antagonist domperidone. Because domperidone blocks peripheral, but not central, DA receptors, and since the entry of threo-dl-p-hydroxymethylphenidate across the blood-brain barrier into the brain is restricted to a great extent, we conclude that stimulation of peripheral DA receptors is primarily involved in the gastric cytoprotection induced by dopamimetics.
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Male SD rats received indomethacin (10 mg/kg) subcutaneously (s.c.), and the small intestine was examined for lesions 24 hr later. Dopamine (1-10 mg/kg) or atropine (3 mg/kg) was administered s.c. twice, 30 min before and 8 hr after indomethacin, while sulpiride (3 mg/kg) and domperidone (3 mg/kg), the dopamine D2 receptor antagonists, or yohimbine (10 mg/kg), the alpha2-adrenoceptor antagonist, were administered s.c. twice, 30 min before each dosing of dopamine. Intestinal motility was measured using a balloon under urethane anesthesia.
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In 71 patients with differentiated thyroid carcinoma, short-term side effects including gastrointestinal complaints, salivary gland swelling with pain, change in taste and headache were retrospectively analyzed. All patients were given domperidone for prevention of gastrointestinal complaints and advised to consume sour foods to promote discharge of radioiodine from the salivary glands. Selected factors possibly affecting the incidence of side effects were dose per body weight, TSH, effective half-life of 131I, sex, age, 131I accumulation into the stomach and salivary glands, and edema prior to radioiodine administration. The factors were evaluated by multivariate analyses.
Arterial hypertension and, less often, postural hypotension are frequently associated with diabetes mellitus, and with diabetic complications and death.
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In this prospective, randomized, double-blinded study, we evaluated the efficacy of the oral antiemetics, granisetron and domperidone, for the prevention of postoperative nausea and vomiting (PONV) in 100 women undergoing major gynecologic surgery. Patients received either granisetron 2 mg or domperidone 20 mg (n = 50 in each group) orally 1 h before surgery. Standardized anesthetic techniques and postoperative analgesia regimens were used. Complete response (defined as no PONV and no administration of rescue antiemetic medication) for 0-3 h after anesthesia was 88% with granisetron and 52% with domperidone; the corresponding incidence for 3-24 h after anesthesia was 86% and 48% (P < 0.05). No clinically important adverse events due to the drugs were observed in any of the groups. In conclusion, the efficacy of preoperative oral granisetron is superior to that of domperidone for the prevention of PONV after major gynecologic surgery.
Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.
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LD alone worsened detrusor overactivity: in particular, a reduction of first urinary sensation, involuntary detrusor contraction threshold (reflex volume) and bladder capacity was observed. L-sulpiride (central and peripheral D2 antagonist) coadministration counteracted the worsening in a dose dependent manner. Domperidone (peripheral D2 antagonist) coadministration failed to determine the same counteraction.
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The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05).
In this large single-center study of patients treated with domperidone, side effects necessitating discontinuing treatment occurred in 12 %. The majority of patients remaining on treatment experienced an improvement in symptoms of gastroparesis, particularly postprandial fullness, nausea, vomiting, and stomach fullness. Thus, domperidone treatment is beneficial for many patients with symptoms of gastroparesis. This study provides needed benefit and risk information concerning treating patients with domperidone. FDA IND Number: 71,089.