The average study quality score was 8.3 out of a possible 15 and the total sample size equaled 1016. Overall, 64% of the studies showed significant efficacy of domperidone on the improvement of symptoms. Sixty percent of the studies showed an efficacy in gastric emptying and 67% of the studies proved the drug effective in reducing hospital admissions.
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The use of psychotherapeutic methods in addition to standard drug therapy improves both the physical and psychological states in patients with GERD and has some impact on a reduction in the magnitude of clinical symptomatology. This may contribute to the prompter recovery of patients and create prerequisites for improving their QL.
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Amphibian declines are now recognized globally. It is also well known that many anurans do not reproduce easily in captivity, especially when held over long periods, or if they require hibernation before breeding. A simple method to induce spawning and subsequent development of large numbers of healthy tadpoles is therefore required to meet research and conservation goals.
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We aimed to describe and assess the evidence from controlled trials on the efficacy and tolerability of pharmacological agents taken on a regular basis to prevent the occurrence of migraine attacks and/or reduce the intensity of such attacks in children with migraine.
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Ninety diabetic gastroparesis patients were randomly assigned to 3 groups. Besides conventional hypoglycemic treatment, the 30 patients in the treated group were given TWK and the 30 in the control group were given Domperidone additionally, while to the 30 in the blank group, no additional drug was given. The clinical efficacy and the changes in level of motilin and gastric emptying rate were observed.
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In food-deprived mice apomorphine injected SC induced a brief (15-30 min) dose-dependent (30-150 micrograms/kg) reduction in food intake. This effect occurred in naive mice as well as in mice habituated to a food deprivation procedure. The anorectic effect of apomorphine (150 micrograms/kg SC) was antagonized by sulpiride (ID50 = 8.6 mg/kg) and by haloperidol (ID50 = 66 micrograms/kg) but domperidone was ineffective (250 micrograms/kg). Mice submitted to a semi-chronic (6 d) blockade of dopamine receptors by haloperidol or injected intracerebroventricularly with 125 micrograms 6-hydroxydopamine 21 d before testing failed to develop a hypersensitivity to the anorectic effect of apomorphine (60 micrograms/kg). Although a single apomorphine injection (5 mg/kg) induced tolerance to the hypothermic effect of a second apomorphine injection of 150 micrograms/kg, it did not modify the anorectic effect. Repeated apomorphine injection (5 x 5 mg/kg) resulted in a slight but significant reduction in apomorphine-induced anorexia. A similarly significant reduction was not observed in mice submitted to repeated injections of dexamphetamine (5 x 5 mg/kg).
This review discusses different pharmacological treatment for gastroparesis patients and describes the potential for drug-drug interactions (DDIs) in some of the combinations that are currently used. Prokinetic agents such as metoclopramide and domperidone are the cornerstone in treatment of gastroparesis. Antiemetic agents such as promethazine and ondansetron are frequently administered to gastroparesis patients to reduce nausea and vomiting. Gastroparesis is prevalent in diabetic patients and therefore antidiabetic agents are also prescribed. Many of these co-administered drugs are metabolized via common drug metabolizing enzymes and this can trigger potential DDIs. The scientific literature was reviewed from the years 1975-2014 for original research articles and reviews that evaluated DDIs in gastroparesis. Many commonly prescribed combinations were predicted to cause potential DDIs in gastroparesis patients. This review will help inform about potential hazardous combinations. This information will hopefully lead to less adverse effects and more successful gastroparesis management.
Increases in both striatal dopamine release and the proportion of the D(2) receptors in the high affinity state (D(2) (High)) accompany the behavioral sensitization to psychostimulants, but it is not known whether the physiological substrate of the interindividual differences locomotor and exploratory behavior is similar. Thus, we examined whether persistently high spontaneous exploratory activity is associated with extracellular dopamine as well as the proportion of D(2) (High) in the striatum. Extracellular dopamine levels were found to be significantly higher in rats with high exploratory activity (high explorers, HE) as compared with low explorers (LE) in baseline conditions as well as after administration of amphetamine (0.5 mg/kg, i.p.). Also, the HE animals had significantly higher proportion of striatal D(2) (High) receptors than the LE-rats (43.8 +/- 4.4% and 22.5 +/- 1.5%, respectively). Thus, the present findings support the notion that concomitant higher extracellular dopamine levels and the proportion of D(2) (High) receptors in the striatum, whether naturally occurring and persistent or pharmacologically induced, are causally related to high behavioral activity.
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All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%), permeation (6806.64 µg) in 24 hrs, flux (86.02 µg /hr/cm(2)) and permeation coefficient of 0.86x10(-2) cm/hr. Values of tensile strength (4.34 kg/mm(2)) and elastic modulus (5.89 kg/cm(2)) revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS.
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The effects of l-stepholidine(l-SPD) on peripheral vascular dopamine DA1 and DA2 receptors were studied using isolated vascular rings in rabbits. It was shown that (1) l-SPD(0.1-10 mumol.L-1) shifted the dose-response curves to the right in a nonparallel fashion and decreased the maximal response (Emax) of both the fenoldopam(FODA, a selective DA1 agonist)-induced and the propyl-buty-dopamine(PBDA, a selective DA2 agonist)-induced vasorelaxation showing a non-competitive antagonistic action. The pD2 values of l-SPD for FODA in the renal, pulmonary and mesenteric arteries were 5.43, 5.48 and 5.58, respectively. The pD2 values for PBDA in the mesenteric and femoral arteries were 5.35 and 5.89, respectively. The potencies of its antagonistic action were comparable to SCH23390, a selective DA1 antagonist, and to domperidone, a selective DA2 antagonist. (2) l-SPD(0.1-100 mumol.L-1) per se was also found to induce slight but dose-related vasorelaxations in the renal and pulmonary arteries displaying its DA1 agonistic activity. Its pD2 values were 4.98 and 5.02, respectively. However, its Emax were considerably smaller than that of FODA. These results suggest that l-SPD is a mixed peripheral DA1 and DA2 receptor antagonists and weak DA1 receptor agonist with pharmacological property of dual action.
A phase II study was performed of oral altretamine in 71 patients with ovarian carcinoma who entered clinical complete remission with CA125 levels less than 35 U/mL after initial or second-line chemotherapy, and relapsed more than 6 months later. Response was compared between standard and CA125-based criteria.
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Our review will focus on treatment options for GP and SIBO with motilin agonists, dopamine receptor antagonists, Ghrelin agonists muscarinic agonists, 5-HT4 receptor agonists, antibiotics, probiotics and herbal formulation such as iberogast. Constipation occurs in the majority of patients with PD and fortunately many treatments are now available. Our review is based on original papers or reviews selected from PUBMED search and Cochrane reviews.
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A novel series of benzamides with a hexahydro-1,4-diazepine or hexahydroazepine ring in the amine moiety were prepared, and their binding affinities for 5-HT3 and dopamine D2 receptors were evaluated. The R isomer of the 1-ethyl-4-methylhexahydro-1,4-diazepinylbenzamide (R)-22 had potent affinity for both receptors. The R-enantiomer of the corresponding 1-ethylhexahydroazepinylbenzamide 28 showed potent affinity for dopamine D2 receptors with reduced affinity for 5-HT3 receptors, while the S isomer was found to be a potent and selective 5-HT3 receptor antagonist.
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The characteristics and functional roles of opioids originally present in vivo (endogenous opioids) in guinea-pig ileum were investigated. The release of endogenous opioids was determined by the inhibitory twitch response evoked by 0.1 Hz stimulation after 10 Hz stimulation (post-tetanic twitch inhibition). The effects of peptidase inhibitors increased the post-tetanic twitch inhibition, prevented by β-funaltrexamine and nor-binaltorphimine, which are selective μ- and κ-opioid receptor subtype antagonists, respectively. Dopamine receptor antagonists (haloperidol, sultopride and domperidone) increased the post-tetanic twitch inhibition. These results suggest that dopamine receptors are involved in modulation of the ileal opioid system, so as to diminish endogenous opioid release by tetanic stimulation, and dopamine antagonists increase the opioid action, that might depend more on the increased release of endogenous opioids. The post-tetanic twitch inhibition was inhibited by adrenalectomy, and showed the supersensitivity of the opioid receptors, resulting from a decrease of endogenous opioids by adrenalectomy. These findings suggest that the increase in morphine-analgesia by adrenalectomy was due to this process. In the presence of naloxone, an opioid antagonist, an increase in basal tension after tetanic stimulation (10 Hz stimulation) (post-tetanic contraction) was observed, and was blocked by spantide, a substance P antagonist, and indomethacin, a prostaglandins-biosynthesis inhibitor. This contraction increased with morphine or peptidase inhibitor exposure, depending on the length of time the ileum was exposed to the morphine or peptidase inhibitor. Post-tetanic contraction might be a useful indicator of the formation of physical dependence to morphine or endogenous opioids in the ileum.
C-1300 murine neuroblastoma ( MNB ) contains the catecholamine biosynthetic pathway. This study investigated manipulation of this pathway for effects on cell growth and survival in tumor-bearing mice, and to correlate these findings with specific membrane-bound dopamine-binding activity. The dopamine antagonists domperidone, pimozide, and spiroperidol inhibited macromolecular synthesis in vitro as demonstrated by decreased [3H]TdR and [14C]leu incorporation in a dose-response fashion; 56, 49, and 43% inhibition was noted at 10(-6) M concentration of each drug, respectively, with no loss of cell viability. Dopamine agonists showed no significant inhibition. Scatchard analysis of dopamine binding was consistent with a single class of receptor sites with a mean concentration of 13.2 +/- 2.0 pmole/g wet weight of tissue and mean dissociation constant (Kd) = 0.69 +/- 0.38 nM, compared to a mean receptor concentration of 28.1 +/- 5.2 pmole/g wet weight of tissue and Kd = 0.38 +/- 0.09 nM in receptor-rich dog caudate nucleus, the normal control. A/J mice injected with 1 X 10(6) tumor cells and treated with daily pimozide or domperidone had a significant increase in disease-free survival when compared to controls (15 versus 8.5 days, P less than 0.001) as well as a significant increase in overall survival (35 versus 25 days, P less than 0.001). These data suggest that dopamine antagonists inhibit macromolecular synthesis in the C-1300 MNB . The inhibition of MNB tumor growth in vivo by dopamine antagonists suggests a specific chemotherapeutic approach to neuroblastoma, possibly mediated by dopamine receptors.
The electrical-mechanical composite measurement method showed an attractive clinical application prospect in gastric motility research and evaluation.
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In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.
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Although both dopamine and dobutamine are potent positive inotropic agents, multiple studies indicate that dopamine may produce a rise in left ventricular (LV) filling pressure, while dobutamine often has the opposite effect. To ascertain the pharmacological and hemodynamic mechanisms responsible for the elevation in LV filling pressure observed with dopamine, we administered incremental infusions (2, 4, and 6 micrograms/kg/min) of dopamine to 18 open-chest, anesthetized dogs in the presence and absence of rauwolscine (selective alpha 2-adrenoceptor antagonist) (n = 7), terazosin (selective alpha 1-antagonist) (n = 6), and domperidone (selective dopamine2 antagonist) (n = 5), while measuring pressures in the LV and left atrium and changes in dimension in the LV short-axis (with ultrasonic piezo crystals). Dobutamine (2, 4, and 6 micrograms/kg/min) was infused in five additional dogs before and after administration of rauwolscine. The time constant of isovolumic pressure decay, peak lengthening rate (mm/sec), LV end-diastolic pressure, and diastolic pressure-dimension relation were computed. A significant elevation in LV end-diastolic pressure and a parallel increase in LV end-diastolic chamber size was observed with dopamine, while a decline in LV end-diastolic pressure occurred with dobutamine. Yet both dopamine and dobutamine caused a dose-related acceleration of pressure decay and augmentation of peak lengthening rate. Furthermore, heart rate declined during the administration of dopamine but rose with dobutamine. In the presence of either rauwolscine or terazosin, dopamine infusion resulted in a positive chronotropic effect and dose-dependent reductions in LV end-diastolic pressure and end-diastolic chamber dimension; arterial pressure fell only after terazosin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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The purpose of this study was to investigate the effects of the calcium channel blocker verapamil in the management of patients with both high blood pressure and orthostatic hypotension. Six hypertensive patients, aged 37-78 years, mean 60.8 +/- 3.2 years, four men and two women, with symptomatic orthostatic hypotension were included in this open study. Verapamil, 240 to 360 mg/day, decreased blood pressure and did not impair orthostatic hypotension with a mean follow-up of 6 months. Blood pressure and heart rate were, in lying and standing position, respectively, as follows: 177.5 +/- 5.9/99.1 +/- 9.9 mm Hg and 81.0 +/- 9.0 beats/min and 120.0 +/- 4.8/83.3 +/- 4.0 mm Hg and 91.0 +/- 9.5 beats/min before treatment; then, 155.8 +/- 5.5/89.1 +/- 4.2 mm Hg and 74.5 +/- 8.6 beats/min and 127.5 +/- 7.3/83.3 +/- 4 mm Hg and 83.0 +/- 9.1 beats/min after verapamil. In three patients with orthostatic hypotension successfully treated by the peripheral dopaminergic antagonist domperidone 60 mg/day, the subsequent introduction of verapamil 240 mg/day did not modify the standing-induced decrease in systolic blood pressure: 46.6 mm Hg under domperidone and 30.0 mm Hg under domperidone plus verapamil. Verapamil increased baroreflex sensitivity from 1.4 to 3.5 ms/mm in all patients. This preliminary study shows the interest of verapamil in the difficult management of hypertension with orthostatic hypotension. It is suggested that verapamil could increase the baroreflex sensitivity in patients with orthostatic hypotension.
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We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatment for symptomatic gastro-oesophageal reflux? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
The purpose of this study was to determine the effect prokinetic drugs inhibiting dopaminergic receptors on gallbladder volume in normal conditions. The study comprised 90 males, aged 20-26 years with duodenal ulcer disease in remission alloted into 3 groups, 30 subject each. The gallbladder volume was determined in group I after placebo or 10 and 20 mg or metoclopramide administration; in group II: placebo or 10 and 20 mg of domperidone and in group III after placebo or 50 and 100 mg of sulphiride administration. Gallbladder motility was assessed ultrasonographically from 15 minutes to 2 hours since placebo or drug administration. The effect of the studied prokinetic drugs in fasting on gallbladder motility was differentiated after metoclopramide no significant changes in gallbladder volume were observed; after domperidone in the dose of 20 mg a slight decrease of gallbladder volume was found, whereas after sulphiryde statistically significant decrease was detected.
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To study the effect of spine surgery (SpS) on gastric function and the efficacy of relevant treatments.
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In an attempt to establish whether, in patients with major depression, dopaminergic receptors are involved in the release of growth hormone (GH) induced by thyrotropin releasing hormone (TRH), eleven subjects were tested with TRH (200 micrograms in an i.v. bolus) with or without concomitant treatment with domperidone (10 mg in an i.v. bolus 10 min before TRH), an antidopaminergic agent which does not readily cross the blood-brain barrier. In 7 out of the 11 patients, TRH strikingly increased GH levels (responders) (the mean peak level was 9 times higher than basal value), whereas it was without effect in the remaining 4 patients (non-responders). When the responders were treated with domperidone before TRH injection, TRH-induced GH increase was still present, but it was significantly lower (the mean peak level was 5.3 times higher than basal value) than in the TRH test (p less than 0.02). These data suggest that the paradoxical response of GH or TRH in patients with major depression involves a dopaminergic mechanism active at sites situated outside the blood-brain barrier.
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Dopamine has been widely used in humans in the management of cardiocirculatory shock, and its inhibitory effect on ventilation has received particular attention in clinical situations more prevalent in the elderly. Dopamine has been extensively studied at the carotid body in adult animals but little is known in aged animals. We investigated the ventilatory responses caused by dopamine in 3 and 24 months old rats.Cumulative intracarotid bolus injections of dopamine were performed in anaesthetised and vagotomised rats, in the absence and in the presence of i.v. infusions of domperidone (23.5-1175 nmol Kg(-1) min(-1)). Airflow (V), tidal volume (V(T)), respiratory rate (f), arterial blood pressure and heart rate were monitored and respiratory minute volume (V(E)) calculated. Basal values of V(E) were lower in 24 months rats (322.9+/-18.8 mL Kg(-1) min(-1)) than in 3 months old rats (442.5+/-24.2 mL Kg(-1) min(-1)), mainly due to reductions in V(T). The dose-dependent decreases caused by dopamine (3-100 nmol) in V(T), f and V(E), were totally prevented by section of the carotid sinus nerve and were not modified by ageing. The maximal % antagonism of the inhibitory effect of dopamine on V(E) caused by domperidone was similar in both 3 (74.6+/-2.7) and 24 (70.7+/-0.8) months old rats. Domperidone alone, increased basal V(E) by 59.6+/-16.6 mL min(-1) Kg(-1), and by 11.8+/-1.2 mL min(-1) Kg(-1), respectively in 3 and 24 months old rats (p<0.01).The inhibitory basal tonus caused by dopamine in ventilation was reduced in aged rats, although the decrease in V(E) caused by its exogenous administration remained unchanged.