Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Buspirone stimulates central 5-hydroxytryptamine (5HT) receptors and brings about the release of prolactin, and there is evidence to suggest that the extent of prolactin release after a challenge with buspirone is an indicator of the sensitivity of central 5HT receptors. Seventeen patients with a diagnosis of non-ulcer dyspepsia, eight normal healthy volunteers, and six patients with peptic ulcer disease were each given a challenge test of 60 mg buspirone orally, and prolactin release over a 3-h period was monitored. The mean prolactin response was significantly greater in patients with non-ulcer dyspepsia than in healthy controls and peptic ulcer disease patients. The results suggest that central 5HT receptors may be supersensitive in non-ulcer dyspepsia.
 ...
PMID:Serotonin supersensitivity: the pathophysiologic basis of non-ulcer dyspepsia? A preliminary report of buspirone/prolactin responses. 235 83

The phylogenetic, therapeutic and experimental evidences suggest that the circulating prolactin levels alter the gastric contractility in experimental animals as well as in patients suffering from gastric dyspepsia. The dopamine antagonists are used in the treatment dysmotility-like dyspepsia and could relieve the dyspeptic symptoms. These drugs are potent stimulants for the release of prolactin. Further, in non-ulcer dyspepsia, a primary dysfunction of pituitary lactotrophs has been proposed. Thus, the dysmotility-like gastric dyspepsia is associated with the deficiency of endogenous prolactin levels so as to reduce gastric contractions. This concept brings a new line of thinking in the pathogenesis of dysmotility-like gastric dyspepsia.
 ...
PMID:Role of prolactin in dysmotility-like gastric dyspepsia. 787 33

The efficacy and tolerability of cisapride (5 mg three times daily) and metoclopramide (10 mg three times daily) were evaluated in a randomized double-blind trial in patients with functional dyspepsia. Sixty patients, equally distributed in the two groups, entered the trial. After 4 weeks of treatment there was a significant improvement of symptom severity versus base line (p < 0.001) in both groups. The percentage of responders (with no or only mild symptoms) was 87% in the cisapride group and 77% in the metoclopramide group (no statistically significant intergroup difference). At the follow-up visit 2 weeks after completion of the trial this response rate was significantly higher in the cisapride group (73%) than in the metoclopramide group (47%) (p < 0.05). Four of the patients receiving cisapride and 2 of the patients receiving metoclopramide reported adverse events. On assessment of extrapyrimidal symptoms, relevant clinical values were found in one patient receiving metoclopramide. Increased prolactin concentrations were observed in seven patients of the metoclopramide group versus only 1 of the cisapride group (p < 0.05). The present data indicate that during the 2 weeks after completion of treatment in patients with functional dyspepsia, cisapride may result in a better, more sustained overall response when compared with metoclopramide.
 ...
PMID:Cisapride versus metoclopramide in the treatment of functional dyspepsia. A double-blind comparative trial. 812 75

In the search for animal models that can replicate some features of functional dyspepsia (FD) patients, we turned our interest to the Flinders Sensitive Line (FSL) rat. Gastric motility disturbances prevalent in FD patients as well as urine corticosterone and plasma prolactin were measured following buspirone challenge. Flinders Resistant Line (FRL) rat was used as control. The results show that the FSL rats have a disturbed gastric motility, reflected as both an increased gastric accommodation rate and gastric volume during gastric distension as well as a delayed gastric emptying, the latter possibly as a consequence of the former. Lipid administration resulted in a significant increase in maximal gastric volume only in the FRL rats. Both the corticosterone response to buspirone and the 24-h urinary output of corticosterone were normal in FSL rats. Similar to FD patients, the FSL rat showed supersensitivity to buspirone in the increase in prolactin release. Although FSL rats show some features similar to a subset of FD patients, the increased gastric accommodation contrasts to the reduced accommodation often seen in FD patients. Further studies are warranted to determine the relevance of this rat strain as a model for FD.
 ...
PMID:Altered neuroendocrine response and gastric dysmotility in the Flinders Sensitive Line rat. 1578 37

The prevalence of psychopathology in patients presenting with functional bowel disorder to the gastroenterology department was determined using formal psychiatric rating scales. There was no evidence of excessive psychiatric disorder compared to a group of patients with peptic ulcer disease. However, greater trait scores for neuroticism and introversion were found in the functional disorder group, together with a greater reporting of life events perceived as negative. Central serotoninergic receptor role in the pathophysiology of functional dyspepsia was assessed using a neuroendocrine challenge test. Buspirone, an azaspirone, stimulates central serotoninergic-1(A) receptors and, as a consequence, releases prolactin, and the extent of prolactin release after the challenge is an indicator of central serotoninergic receptor sensitivity. The mean prolactin response was significantly greater in patients with functional dyspepsia than in healthy controls and peptic ulcer disease patients. The sensitivity of the central serotoninergic receptors was also highly correlated with the degree of delayed solid phase gastric emptying assessed scintigraphically. Finally, dyspeptic symptoms can be reproduced in patients by an intravenous cholecystokinin infusion and severity of response was analysed using a visual analogue scale.
 ...
PMID:Serotonin and physical illness: focus on non-ulcer dyspepsia. 2228 64

Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist in late-stage clinical development for the treatment of bipolar disorder (manic/mixed and depressive episodes), as well as for schizophrenia, and as an adjunctive agent for the treatment of major depressive disorder. Three phase 2 or 3, 3-week, randomized controlled trials in bipolar mania or mixed episodes have been completed and reported as poster presentations or in press releases by the manufacturer. Superiority over placebo on the Young Mania Rating Scale total score was evidenced for daily doses of cariprazine 3-12 mg/day. In short-term randomized controlled trials, cariprazine does not appear to adversely impact metabolic variables, prolactin, or the electrocardiogram (ECG) QT interval. The most commonly encountered adverse events in the mania trials were extrapyramidal disorder, akathisia, insomnia, vomiting, restlessness, sedation, vision blurred, and pain in extremity in the phase 2 trial where this was presented in a poster, and akathisia, extrapyramidal disorder, tremor, dyspepsia, vomiting, dizziness, diarrhea, somnolence, restlessness, and pyrexia for the phase 3 trial where this was presented in a poster. With the exception of akathisia and extrapyramidal disorder, the differences in incidence versus placebo for these events were generally small. If approved by regulatory authorities, cariprazine would join aripiprazole as the second dopamine receptor partial agonist antipsychotic available for clinical use in persons with bipolar mania or mixed episodes. Cariprazine differs from aripiprazole in terms of dopamine D3 receptor selectivity. Further studies would be helpful to discern the distinguishing features of cariprazine from other antimanic agents.
 ...
PMID:Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy. 2336 32

Cariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-amine hydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist-partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3-12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine's partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatment-emergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date.
...
PMID:Clinical potential of cariprazine in the treatment of acute mania. 2404 86