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Several studies have shown the relationship between gastro-oesophageal reflux, bronchial asthma and chronic nocturnal cough and this should not be neglected, particularly in patients who present an unfavourable development in spite of conventional treatment. For diagnosis of gastroesophageal reflux, amongst other investigations, esophageal gammagraphy of swallowing, that detects alterations in the mobility of the oesophagus, secondary to a possible oesophagitis. The objective of this study was to evaluate the clinical progress and gammagraphy of a group of children with chronic predominantly nocturnal cough (with or without bronchial asthma) with initially pathological esophageal gammagraphy, after three months of treatment with gastrokinetic drugs (cisapride against domperidone) and postural dietetic limits, in comparison with a reference group who, although having followed the limits in question had not received the pharmacological treatment. From the clinical viewpoint, cough disappeared in 64.5% of cases without significant statistical differences between the two groups. Gammagraphy became normal in 20/55 cases, improved in 10/55 cases and was unchanged in 25/55. Although there was no significant difference, gammagraphy development was better in children who received domperidone. The agreement between clinical progress and gammagraphy was 60% with a large number of false positives in the gammagraphy. We believe that the simple introduction of the postural-dietetic measures may improve the clinical control in the type of patients who present with a chronic nocturnally predominant cough that does not yield to conventional treatment.
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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.
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Transdermal absorption of a series of antiemetics (alizapride, bromopride, clebopride, domperidone, metoclopramide, metopimazine, and scopolamine) was studied in vitro with the skin of hairless rats as the membrane. The aim of the study was to determine the permeation parameters [transdermal permeability rate constant (Kp), lag time, and flux] as a measure of the intrinsic permeability of these drugs across the skin, with a view to predicting their potential therapeutic formulation in Transdermal Therapeutic Systems. A linear correlation was established between the log Kp values corresponding to the antiemetics studied and their melting point (r = 0.8120, p < 0.05). The logarithm of Kp for the antiemetics studied can be predicted from the logarithm of the intrinsic partition coefficient (n-octanol-water) by a parabolic function (r = 0.9284, p < 0.01). Bromopride showed the shortest lag time (19.73 h), whereas clebopride was the most suitable drug as a candidate for formulation in transdermal delivery systems.
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We studied 39 patients presenting parkinsonian signs. Based on clinical examination, 23 subjects (7 f, 16 m, mean age (SD) 59.2 (7.8) years were diagnosed as having probable PD, and 16 patients (5 f, 11 m, mean age 72 (7.6) yrs, p < 0.001) as having probable PS. In the PD group, mean Hoehn and Yahr degree of severity was 2.7 (1.1), mean duration of the disease 9.5 (6.2) yrs, mean duration of L-DOPA treatment (20 patients) 6.7 (5.5) yrs. In the PS group, the respective values of Hoehn and Yahr were 3.3 (0.9), mean duration of the disease 6.2 (4.1) yrs and mean duration of L-DOPA treatment (10 patients) 1.6 (1.1) yrs. After an overnight withdrawal of all other dopaminergic medication, a single subcutaneous dose of Apomorphine hydrochloride solution corresponding to 0.05 mg per kg of weight was administered. Domperidone was given 60 mg daily prior to the testing to avoid undesirable peripheral effects of APO. 20 minutes after APO administration, we noted a marked clinical improvement i.e. at least 30% decrease of pre-treatment motor score values on Columbina University Rating Scale (CURS) in 19 of 23 PD and in one of 16 PS patients. In the PD group, the difference between mean CURS values, 30.7 (19.5) before and 14.7 (10.3) after APO was highly significant (p < 0.001). In the PS group, only a slight posttreatment CURS decrease was found, 39.8 (17.5) before and 37.8 (17.5) after APO (p < 0.05).
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Intraventricular administration of haloperidol or chlorpromazine produces catalepsy and blocks apomorphine-induced stereotypic behavior. Low intraventricular doses of domperidone, sulpiride and spiperone, equally cataleptogenic as haloperidol or chlorpromazine, augment rather than diminish stereotypic behavior produced by subsequent apomorphine treatment. The resultant stereotypic behavior continues even while the animal is in a rigid cataleptic posture and is marked by persistent gnawing and licking. Prior to the induction of catalepsy and after recovery from it, mice display the entire range of typical apomorphine-induced behavior including sniffing, climbing, gnawing, and licking. This animal model may be related to the clinical observation of the coexistence of tardive dyskinesia and drug-induced Parkinsonism in individual patients.
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The signaling enzyme phospholipase D (PLD) and the lipid second messenger it generates, phosphatidic acid (PA), are implicated in many cell biological processes, including Ras activation, cell spreading, stress fiber formation, chemotaxis, and membrane vesicle trafficking. PLD production of PA is inhibited by the primary alcohol 1-butanol, which has thus been widely employed to identify PLD/PA-driven processes. However, 1-butanol does not always effectively reduce PA accumulation, and its use may result in PLD-independent deleterious effects. Consequently, identification of potent specific small-molecule PLD inhibitors would be an important advance for the field. We examine one such here, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), which was identified recently in an in vitro chemical screen for PLD2 inhibitors, and show that it rapidly blocks in vivo PA production with subnanomolar potency. We were surprised to find that several biological processes blocked by 1-butanol are not affected by FIPI, suggesting the need for re-evaluation of proposed roles for PLD. However, FIPI does inhibit PLD regulation of F-actin cytoskeleton reorganization, cell spreading, and chemotaxis, indicating potential utility for it as a therapeutic for autoimmunity and cancer metastasis.
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Dose-dependent relaxations were induced by dopamine in human pulmonary arteries that had been contracted with prostaglandin F2 alpha without alpha-adrenergic blocking agents. The dopamine-induced relaxation was inhibited by haloperidol and fluphenazine, but not by domperidone, suggesting that this relaxation was mediated via DA1 receptors.
These data indicated that slow oscillations in vaginal blood flow from rodents may be utilized as an animal model of female sexual arousal. Changes in these oscillations are driven by the central nervous system and modulated by the autonomic nervous system.
In the present study, we investigated the existence of a back-regulation of the catecholamine-degrading enzyme monoamine oxidase (MAO)-A by dopamine in rat renal cells. In proximal tubule cells, MAO-A expression was not modified after dopamine receptor stimulation. In contrast, in mesangial cells, enzyme assay and Western blots showed that MAO activity and protein increased by approximately 80% after 48-h incubation with the D(2)-like receptor agonist bromocriptine and quinpirole but not with the D(1)-like receptor agonist SKF-38393. This effect was prevented by the D(2)-receptor antagonist sulpiride and domperidone. The increase in MAO-A protein was preceded by an augmentation of MAO-A mRNA that was prevented by the transcriptional inhibitor actinomycin D. Bromocriptine effect was mimicked by the PKA inhibitor H89 and inhibited by the PKA activator 8-bromo-cAMP. These results show for the first time the existence of a dopamine-dependent MAO-A regulation involving D(2)-like receptors, inhibition of the cAMP-PKA pathway, and an ex novo enzyme synthesis.
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Non-acid GERC had the similar cough character, cough symptom score, and capsaicin cough sensitivity to acid GERC. However, non-acid GERC had less frequent regurgitation (15.8% vs 57.1%, χ(2) = 13.346, P = 0.000) and heartburn (7.9% vs 32.7%, χ(2) = 7.686, P = 0.006), and lower GerdQ score (7.4 ± 1.4 vs 10.6 ± 2.1, t = -6.700, P = 0.003) than acid GERC. Moreover, MII-pH revealed more weakly acidic reflux episodes, gas reflux episodes and a higher symptom association probability (SAP) for non-acid reflux but lower DeMeester score, acidic reflux episodes and SAP for acid reflux in non-acid GERC than in acid GERC. Non-acid GERC usually responded to the standard anti-reflux therapy but with delayed cough resolution or attenuation when compared with acid GERC. Fewer patients with non-acid GERC needed an augmented acid suppressive therapy or treatment with baclofen.
The excretion and metabolism of the novel gastrokinetic and antinauseant drug domperidone were studied after oral administration of the 14C-labelled compound to rats, dogs and man, and after intravenous administration to rats and dogs. Excretion of the radioactivity was almost complete within four days. In the three species, the radioactivity was excreted for the greater part with the faeces. Biliary excretion of the radioactivity amounted to 65% of the dose 24 hours after intravenous administration in rats. Unchanged domperidone as determined by radioimmunoassay, accounted in urine for 0.3% in dogs, 0.4% in man, and in faeces for 9% in dogs and 7% in man. The main metabolic pathways of domperidone in the three species were the aromatic hydroxylation at the benzimidazolone moiety, resulting in hydroxy-domperidone -the main faecal metabolite-, and the oxidative N-dealkylation at the piperidine nitrogen, resulting in 2,3-dihydro-2-oxo-1H-benzamidazole-1-propanoic acid the major radioactive urinary metabolite- and 5-chloro-4-piperidinyl-1,3-dihydro-benzimidazol-2-one. In urine the two first metabolites were present partly as conjugates. A mass balance for the major metabolites in urine, faeces, bile and plasma samples was made up after radio-HPLC (reverse-phase HPLC with on-line radioactivity detection) of various extracts. Only minor species differences were detected.
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Ketoconazole tripled the plasma concentrations of domperidone. Domperidone and ketoconazole increased QT(c) F in men, whether given together or separately. The effect of domperidone alone was below the level of clinical importance. The negative result in women is unexplained.
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The present study was designed to investigate the presence of dopamine D2-like receptor sites in the main trunk of the human, rabbit and rat pulmonary artery using combined radioligand binding and light microscope autoradiography techniques. [3H]Spiroperidol was used as a ligand. The presence and the localisation of the sympathetic neuroeffector plexus were also studied using catecholamine histofluorescence techniques. Radioligand binding experiments demonstrated the labelling of a population of dopamine D2-like receptors in sections of human and rabbit pulmonary arteries by [3H]spiroperidol. No specific binding occurred in sections of the rat pulmonary artery. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia, including the adventitia-media border, of the human and rabbit pulmonary arteries. No specific silver grains were found in sections of the rat pulmonary artery. Studies on the pharmacological characterisation of [3H]spiroperidol binding sites in the human and rabbit pulmonary arteries showed that they are sensitive primarily to domperidone, haloperidol, (-)-sulpiride or bromocriptine, and to a lesser extent to n-propylnorapomorphine, quinpirole or clozapine displacement. This suggests that [3H]spiroperidol binding sites in the pulmonary artery probably belong to the dopamine D2 receptor subtype. Catecholamine histofluorescence techniques revealed a rich plexus of fluorescent adventitial and adventitial-medial nerve fibres in the human and to a lesser extent in the rabbit pulmonary artery. Comparison of the localisation of dopamine D2-like receptor sites and of the sympathetic neuroeffector plexus in the pulmonary artery, suggests a possible prejunctional localisation of these sites.
The action of dopamine agonists (apomorphine, bromocriptine, pergolide and quinpirole) on the bradycardia induced in vivo by electrical stimulation of the vagus nerves was studied in pithed rats pretreated with atenolol. The dopamine agonists decreased significantly the vagal-induced but not the acetylcholine-induced bradycardia. The first effect was blocked by (S)-sulpiride or domperidone but not by yohimbine, prazosin or SCH 23390. Both effects were antagonized by methylatropine. The data suggest the presence of presynaptic and/or ganglionic dopamine DA2 receptors in the parasympathetic innervation of the rat heart, stimulation of which inhibits the release of acetylcholine.
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Our data demonstrate that the clinically relevant cardiotoxicity of domperidone and metoclopramide corresponds to a rather potent and local anesthetic-like inhibition of cardiac Na channels including Nav1.5. These data suggest that Nav1.5 might be a hitherto unrecognized molecular mechanism of some cardiovascular side effects, for example, malignant arrhythmias of prokinetic and antiemetic agents.
Motor complications arising after long-term treatment with levodopa remain one of the main challenges in the treatment of patients with Parkinson's disease (PD). Monotherapy with dopamine agonists may delay the onset of motor complications or reduce their severity when added to levodopa treatment. Here, we retrospectively analyzed data from 62 patients with advanced PD who presented with moderate to severe response fluctuations in whom we increased the dose of oral treatment with pergolide beyond 4.5mg daily. Patients had been treated with levodopa for 10.7+/-4.8 years. Pergolide was increased to 8.2+/-4.3 mg per day over a median titration period of 13.5 weeks. Mean daily dose of levodopa prior to pergolide high-dose treatment was 733+/-468 mg and decreased to 348+/-186 mg after pergolide titration. The duration of OFF times decreased from 7.3+/-3.8 to 1.7+/-0.9 h per day (p < 0.001) measured by patients' diaries. Dyskinesias, present for 5.0+/-3.3 h per day at baseline, were reduced to 1.4+/-0.8 h per day (p < 0.001) and the total daily duration of motor fluctuations (off-time duration plus dyskinesia duration) decreased from 10.5+/-7.0 to 2.8+/-2.2 h (p < 0.001). There was a significant improvement in parkinsonian symptoms (baseline to endpoint reduction of UPDRS III from a median of 36 to 8; p < 0.001). To reduce gastrointestinal side effects 23 patients required concomitant treatment with domperidone. Seven patients developed hallucinations during the titration period, six patients required treatment with clozapine. Our data indicate that increasing the dose of pergolide above 5mg per day can dramatically reduce the need for levodopa, motor fluctuations and severity of clinical symptoms. Controlled trials are needed to further substantiate the efficacy and safety of this treatment strategy.
The 32 rats were randomly divided into normal group, model group, Chaihu Shugansan group and domperidone group (n = 8). The functional dyspepsia model was established by constantly squeezing their tails and mean while saline, Chaihu Shugansan decoction and domperidone suspension were administered respectively to 4 groups by gavage. The expression of gastrin and somatostatin in hypothalamus and gastric antrum of rats by immunohistochemical were detected 3 weeks later.
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Scopolamine hydrobromide (hyoscine) is an antimuscarinic drug which is primarily used in the prophylaxis and treatment of motion sickness and as a premedication to dry bronchial and salivary secretions. In acute overdosage, the main clinical problem is central nervous system (CNS) depression. In Australia, tablets containing scopolamine hydrobromide 0.3 mg are available over the counter in packs of ten. The recommended dose for adults is one to two tablets as a single dose, repeated four to six hours later, if required. The maximum dose stated on the pack is four tablets over a 24-hour period with a caution regarding drowsiness and blurred vision. We describe a patient who presented with symptoms of anticholinergic syndrome secondary to an unintentional overdose of scopolamine. Whilst at work, the patient noticed that he had forgotten his prescribed medication, domperidone, at home; a friend gave him some travel sickness medication which contained scopolamine for relief of nausea. On a previous occasion, he had experienced a similar, less severe reaction with another anticholinergic agent, loperamide. This report highlights the need to consider nonprescription products, ie, over the counter medications, herbal/nutritional supplements as causes of anticholinergic syndrome when a patient presents with symptoms suggestive of this diagnosis.
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The authors describe the gastro-kinetic drugs that act on functional dyspepsia including metoclopramide, domperidone, clebopride cisapride. Moreover, in some forms of non-ulcer dyspepsia it is useful to give sulglicotide, a cytoprotective drug that has been shown to induce marked improvement of clinical symptoms and endoscopic findings.
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The role of D2/D3 receptors in striatum was electrophysiologically examined in vitro in chloralose-anesthetized rats. In addition, in vitro patch clamp method with rat brain slices was followed. Stimulations of the substantia nigra pars compacta (SN) in vivo elicited spike generation which was inhibited by microiontophoretically applied domperidone, a D2 antagonist. These domperidone-sensitive neurons were activated by microiontophoretic application of D2 agonists such as talipexole, quinpirole and bromocriptine as well as the D2 agonist, 7-OH-DPAT. They were also excited by either intravenous injection of bromocriptine or talipexole in a dose-dependent manner. Furthermore, the SN-induced increases in neuronal firing were blocked during microiontophoretic application of domperidone. In patch clamp whole-cell recording large-sized cells, identified visually under Ramanosky microscope, were depolarized with repetitive firing on bath application of talipexole and 7-OH-DPAT at a current clamp mode. Talipexole-induced depolarization in the large-sized cell was similarly observed in the presence of TTX and high Mg2+ in Ca(2+)-free physiological solution. In contrast, the medium-sized cells were hyperpolarized on bath application of talipexole without being affected by 7-OH-DPAT. These findings suggest that the large-sized cells, which were presumably cholinergic interneurons, are activated by dopamine derived from the SN via D2 and/or D3 receptors, while the medium-sized cells are inhibited by dopamine via D2 receptors.
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Intracellular recordings were obtained from CA1 neurons of rat hippocampal slices preparation. Dopamine applied by perfusion (10(-5)-10(-7) M), microdrop (10(-4) M) and iontophoresis (+80, +200 nA balanced current) inhibited "spontaneous" and evoked action potentials. An increase in current injection restored the evoked action potentials which appeared unmodified. Membrane potential was not modified in 60% of the neurons; in the remaining ones, a slow depolarization was observed. Membrane resistance, measured at rest, was not modified by dopamine. Calcium-mediated events such as bursting activity and afterhyperpolarization, mainly in the late component, were also attenuated by the catecholamine. These effects were antagonized by domperidone, a dopaminergic antagonist. Calcium spikes, evoked in tetrodotoxin- and tetraethylammonium-poisoned slices, were reversibly inhibited by dopamine. Since an increase in the amplitude of a depolarizing pulse of injected current was able to evoke both sodium and calcium action potentials suppressed by dopamine without change in shape or duration, it is concluded that this catecholamine depresses cellular excitability by altering the interaction between membrane voltage and sodium and calcium entry and the subsequent increase in potassium conductance.
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Flos Lonicerae Japonicae is a well-known herb of traditional Chinese medicine that has been used for heat-clearing, detoxification, anti-inflammation, throat pain and gastro-intestinal (GI) disorder. In order to verify the effect of Flos Lonicerae Japonicae on GI disorder, we investigated the prokinetic effect of GC-7101 on GI motility function.
Nine patients with hyperprolactinemia and one patient with pituitary microadenona were observed for 6 years. They were induced by administration of domperidone. The clinical characteristic of the 9 patients was summarized and analysed. The results suggest that prescribe domperidone for fertile women should pay more attention to its adverse effect on inducing hyperprolactinemia and even pituitary microadenona.
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Gastroesophageal reflux (GOR) is a major cause of morbidity and failure to thrive particularly in neurologically impaired children. Clinical manifestations of GOR in children range from regurgitation, food refusal, irritability, failure to thrive, hematemesis, wheezing and aspiration pneumonia, apnoea and apparent life threatening events in infants to clinically silent reflux. Although, no one test is always best to diagnose GOR, 24 hour esophageal pH monitoring remains the 'gold standard' for diagnosis. Barium radiography is useful for the diagnosis of associated anatomical abnormalities and endoscopy enables a histological diagnosis of esophagitis. Therapy for gastroesophageal reflux disease is now well established. Proper positioning of the baby and thickening of feeds is beneficial in uncomplicated GOR. Prokinetic agents like cisapride should be tried if dietary management and antacids are ineffective. Metoclopramide or domperidone may be tried in neurologically impaired children. H2-receptor antagonists are indicated in GOR complicated by esophagitis. Ranitidine is regarded to be more potent. Cimetidine has additional spectrum of adverse effects and sufficient information is not available on famotidine. Omeprazole has been shown to be effective in treating GOR-esophagitis resistant to H2 antagonist therapy even in high risk patients.
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The goal of this study was to develop a new approach to study the pharmacology of the dopamine D(4) receptor that could be used in comparative studies with dopamine D(2) and D(3) receptors. Stable HEK-293 cell lines co-expressing recombinant human D(2L), D(3) or D(4) receptors along with Galpha(qo5) cDNA were prepared. Dopamine induced a robust, transient calcium signal in these cell lines with EC(50)s for D(2L), D(3) and D(4) of 18.0, 11.9 and 2.2 nM, respectively. Reported D(4)-selective agonists CP226269 and PD168077 were potent, partial D(4) agonists exhibiting 31-1700-fold selectivity for D(4) over D(3) or D(2). Non-selective D(2)-like agonists apomorphine and quinpirole showed full efficacy but did not discriminate across the three receptors. D(3)-selective agonists 7-hydroxy-DPAT and PD128907 were potent but non-selective D(2)-like agonists. The reported D(3) partial agonist BP-897 exhibited minimal agonist activity at D(3) but was a potent D(3) antagonist and a partial D(4) agonist. Other D(2)-like antagonists, haloperidol, clozapine, and domperidone showed concentration-dependent inhibition of dopamine responses at all three receptors with K(i) ranging from 0.05 to 48.3 nM. The D(3) selective antagonist S33084 and D(4)-selective antagonist L-745870 were highly selective for D(3) and D(4) receptors with K(b) of 0.7 and 0.1 nM, respectively. Stable co-expression of D(2)-like receptors with chimeric Galpha(qo5) proteins in HEK-293 cells is an efficient method to study receptor activation in a common cellular background and an efficient method for direct comparison of ligand affinity and efficacy across human D(2L), D(3) and D(4) receptors.
It is well established that stress causes a rise in plasma prolactin (PRL) levels of male or cycling female rats. In lactating animals, the pituitary PRL response to stress is not well understood. Therefore, the purpose of the present study was to analyze this question in lactating rats having low or elevated prestress plasma PRL levels. The animals were exposed to ether, formalin or restraint, and plasma PRL and corticosterone levels were determined. In mothers continually together with their pups, plasma PRL levels decreased significantly after exposure to ether vapor or injection of formalin under the skin. At the same time, both agents caused a significant rise in blood corticosterone concentrations. Lactating rats isolated for 4 h had very low levels of PRL before application of stress. However, neither formalin nor restraint caused any elevation in their plasma PRL levels although both interventions increased blood corticosterone concentrations. Lactating mothers receiving formalin after a 30-min suckling stimulus preceded by 4 h isolation did not show appreciable changes in pituitary PRL secretion following the administration of formalin. For information on the mechanism of the effect of stress on PRL, lactating rats were pretreated with the dopamine receptor antagonist domperidone (injecting 80 micrograms/kg body weight) or were adrenalectomized 7 days prior to exposure to stress. The very high levels of PRL caused by domperidone decreased markedly in animals subjected to restraint stress. Administration of formalin to adrenalectomized lactating rats continually together with their litter caused a slight immediate decrease, followed by a transitory elevation and a subsequent small second decrease in blood PRL concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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Sixty SD rats were randomly divided into 6 groups: control, model, herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan (decoction for relieving liver stagnation) and Domperidon, with 10 rats in each group. The FD model was established by applying chronic restraint stress + excessive fatigue + irregular food + tail clipping+ shaking for 21 consecutive days. Moxibustion (herbal cake-separated or moxa-cone) was applied to bilateral "Ganshu" (BL 18), "Pishu" (BL 20) and "Weishu" (BL 21), or "Zhangmen"(LR 13), "Qimen" (LR 14) and "Zhongwan" (CV 12) for 30 min, once daily for 14 d. For rats of the two medication groups, Xiaoyaosan [1 mL (2 g)/100 g] and Domperidone [1 mL (0.3 g)/100 g] were administrated by gavage, respectively. The contents of 5-HT, DA and NE in the hypothalamus tissue were detected by high performance liquid Phrnm.tnrnh,
The different roles of D1 and D2 dopamine receptors in LUT behavior have been demonstrated in animal studies. In particular D2 selective agonists and D1 selective antagonists seem to produce a reduction of the bladder capacity in conscious rats. This finding has never been confirmed in human studies. Thus, in this study we investigated the role of D1 and D2 agonists/antagonists on LUT behavior in patients with PD.
We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron. These had to be randomised controlled clinical studies into the known indications for metoclopramide and domperidone for prevention and treatment of nausea and vomiting. Two reviewers independently selected articles based on the title and abstract, then assessed for eligibility based on the full texts.
In order to understand how histamine-sensitized airways may react to exogenous dopamine, we investigated the effect of histamine treatment on the dopamine-induced contractions of canine tracheal smooth muscle. The results showed that preconstricting muscle strips with histamine (10(-6) M to 10(-4) M) not only increased the amplitude of dopamine-induced contraction, but also lowered the concentration of dopamine required to provoke contraction from 10(-4) M to 10(-6) M. In muscle strips desensitized by repeated challenges of 10(-3) M dopamine, a 15-min treatment with 10(-4) M histamine transiently restored the response. The restored contractions were decreased by the dopaminergic antagonist, domperidone, and the alpha 2-adrenoceptor antagonist, yohimbine, and increased by the beta 1-adrenoceptor antagonist, atenolol. It is concluded that in addition to its role in mediating airway constriction, histamine can promote and enhance the contractile response of canine tracheal smooth muscle to dopamine. Histamine treatment restored the dopamine response of desensitized tracheal muscle with resensitization of the adrenoceptors.