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At least 919 records · Page 51Linked to original sources
PubMed1996

Octreotide in malignant intestinal obstruction.

Octreotide has proved an effective agent in the palliation of refractory malignant intestinal obstruction. This may be achieved through a pro-absorptive effect on the small bowel mucosa, an effect on improving gastrointestinal motility, by a reduction in gastrointestinal hormone levels and by a direct anti-neoplastic effect on the obstructing tumour. The simple route of administration of octreotide and the paucity of side effects reported in two recent studies should make the physician consider its use in this particularly distressing complication of advanced cancer.

Animals↗
PubMed1996

[Pharmacologic and clinical differentiation of prokinetic drugs].

In the treatment of gastrointestinal motility disorders 3 prokinetic agents are principally available. They are differentiated from their pharmacological mode of action, their clinical efficacy and tolerability. Metroclopramide is an antidopaminergic benzamide with mainly antiemetic effects and minor prokinetic efficacy in the GI-Tract. Domperidon is a pure dopaminantagonist. It accelerates gastric emptying but has less effect on bowel motility. Cisapride stimulates indirect the secretion of acetylcholine and acts via 5 HT-receptors selective at the plexus myentericus. These pharmacological differences have clinical relevance: metoclopramide and domperidon could not consistently prove efficacy in functional dyspepsia and GORD. In addition the data in other indications are rare. Only cisapride has shown significant responder rates in controlled studies in the treatment of gastrointestinal motility disorders particularly in long term treatment. As concerns tolerability cisapride presents a progress by its selective mode of action in contrast to the agents crossing the blood-brain-barrier.

Adult↗
PubMed2003

Design and synthesis of orally active benzamide derivatives as potent serotonin 4 receptor agonist.

A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the 1-position on the piperidine ring was synthesized. They were evaluated for serotonin 4 (5-HT(4)) receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (1a, Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a. These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability.

Administration, Oral↗
PubMed1995

Gastrointestinal function in chronic renal failure.

Feeding problems, anorexia and vomiting are common in infants and children with chronic renal failure (CRF), and play a major role in the growth failure often found in this condition. However, the gastroenterological and nutritional aspects of CRF in children have received little attention, hence therapeutic interventions are usually empirical and often ineffective. Gastritis, duodenitis and peptic ulcer are often found in adults with CRF on regular haemodialysis and following renal transplantation. Despite persistent hypergastrinaemia, gastric acid secretion is decreased rather than increased in most of these patients, and active peptic disease appears to be promoted by the removal of the acid output inhibition (neutralisation of gastric acid by ammonia) that follows active treatment. Helicobacter pylori, on the other hand, does not seem to play a significant role in the pathogenesis of peptic disease in CRF. Gastro-oesophageal reflux has been found in about 70% of infants and children with CRF suffering from vomiting and feeding problems, and thus appears to be a major problem in these patients. In a number of symptomatic patients with CRF, gastric dysrhythmias and delayed gastric emptying have also been found; hence there appears to be a complex disorder of gastrointestinal motility in CRF. Serum levels of several polypeptide hormones involved in the modulation of gastrointestinal motility [e.g. gastrin, cholecystokinin (CCK), neurotensin] and the regulation of hunger and satiety (e.g. glucagon, CCK) are significantly raised as a consequence of renal insufficiency, and can be reverted to normal by renal transplantation. Furthermore, several other humoral abnormalities (e.g. hypercalcaemia, hypokalaemia, acidosis, etc.) are not uncommon in CRF. By directly affecting the smooth muscle of the gut or stimulating particular areas within the central nervous system, all these humoral alterations may well play a major role in the gastrointestinal dysmotility, anorexia, nausea and vomiting in patients with CRF. Specific pharmacological and nutritional interventions should thus be considered for the treatment of vomiting and feeding problems in CRF.

Child↗
PubMed2001

Effect of a tachykinin NK(2) receptor antagonist, nepadutant, on cardiovascular and gastrointestinal function in rats and dogs.

The effect of the tachykinin NK(2) receptor antagonist, nepadutant (MEN 11420 or (c[[(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta)])) was assessed on cardiovascular function (unanaesthetized rats and anaesthetized dogs) and gastrointestinal motor activity (fasted unanaesthetized dogs). The selective tachykinin NK(2) receptor agonist, [betaAla(8)]neurokinin A (4-10), up to 100 nmol/kg, i.v., did not produce changes on mean blood pressure or heart rate in unanaesthetized rats. Nepadutant did not affect blood pressure and heart rate up to 10 micromol/kg, whereas saredutant (SR 48968 or ((S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] benzamide), a nonpeptide antagonist, produced a transient reduction of mean blood pressure and heart rate. Nepadutant up to 20 micromol/kg, i.v. neither caused changes of cardiovascular and respiratory parameters in anaesthetized dogs nor induced any changes in left ventricular systolic pressure, left ventricular dP/dt or of electrocardiogram (lead II) waveforms. Intravenous administration of neurokinin A (9 nmol/kg) in unanaesthetized dogs stimulated gastrointestinal motility for 20-25 min. Nepadutant at 0.1 micromol/kg suppressed the stimulant effects of neurokinin A but, up to a dose of 10 micromol/kg, did not produce significant changes in the basal migrating motor complexes. We conclude that tachykinin NK(2) receptors do not participate in the physiologic regulation of resting cardiovascular and respiratory functions and that they do not regulate the fasted pattern of gastrointestinal motility. The cardiovascular changes induced by the nonpeptide tachykinin NK(2) receptor antagonist, saredutant, likely arise from nonspecific effects unrelated to tachykinin NK(2) receptor blockade.

Animals↗
PubMed2002

Ileojejunal transposition delays gastric emptying and decreases fecal water content in dogs with total colectomy.

PURPOSE: The aim of the study was to investigate the effect of ileojejunal transposition, in which the distal ileum is interposed isoperistaltically into the proximal jejunum, on gastric emptying, gastrointestinal motility, and fecal water content in dogs with total colectomy. METHODS: Dogs were divided into three groups: dogs with intact colons (control), total colectomy alone (sham operated group), or total colectomy and ileojejunal transposition group. The alimentary tract was reconstructed by ileal J-pouch-rectal anastomosis. Gastric emptying was measured by a validated freeze-drying method, and gastrointestinal motility was measured by strain gauge force transducers. Plasma peptide YY was measured by specific radioimmunoassay. Fecal water content was measured in dogs with total colectomy. RESULTS: Gastric emptying of solids in the ileojejunal transposition group was delayed longer than 120 minutes after meal ingestion compared with that in the sham operated group. The duration of the digestive state was prolonged in the ileojejunal transposition group, only when compared with the control group. Plasma peptide YY was increased in the ileojejunal transposition group compared with the sham operated group. Fecal water content was decreased in the ileojejunal transposition group compared with the sham operated group. CONCLUSIONS: Ileojejunal transposition delays gastric emptying of solids and decreases fecal water content in dogs with total colectomy, indicating that ileojejunal transposition might be able to improve intractable watery diarrhea after total colectomy.

Animals↗
PubMed1995

[Influence of stimulating zusanli with moxibustion of different quality and quantity on gastrointestinal motor function of reserpinized rats].

This article is focused on the observation of changes in body temperature, body weight, cholinesterase activity in blood, and gastrointestinal motility of reserpinized rats treated by stimulating Zusanli (ST 36) with moxibustion of different quality. (mugwort floss or pipe tobacco) and quantity (strong stimulation or weak stimulation). The experiment shows that better results are achieved with moxibustion not by burning tobacco; the result of strong stimulation with moxa-sticks is better than that of weak stimulation with the same material. Strong stimulation with moxa-sticks can obviously increase the activity of cholinesterase (P < 0.05), inhibit hyperactive gastrointestinal motility (P < 0.05), maintain normal body temperature (P < 0.05), and prevent body weight lossing. All these show that therapeutic results of moxibustion are closely related to the quality and quantity of moxibustion.

Animals↗
PubMed2005

Preliminary pharmacological studies on Piper chaba stem bark.

Piper chaba Hunter (Piperaceae) is a common pepper in the southern part of Bangladesh. Various parts of this plant have been extensively used in different traditional formulations including ayurveda. In order to rationalize the ethnomedical uses of this plant in a number of ailments, the methanol extract of the stem bark was subjected to preliminary evaluation for analgesic, anti-inflammatory, diuretic, anti-diarrhoeal, effect on gastrointestinal motility and CNS depressant activity in mice and rat at 125, 250 and 500 mg/kg body weight doses. The extract at given doses significantly and dose dependently reduced the frequency of acetic acid induced writhing in mice, prolonged the tail flicking latency in mice, reduced Carrageenan-induced paw edema volume in rat, delayed the onset as well as reduced the frequency of castor oil induced diarrhoeal episodes in mice, decreased gastrointestinal motility as assessed by the charcoal motility test in mice and prolonged pentobarbitone induced sleeping time in mice. However at the same doses, the extract exhibited moderate diuretic activity only at the highest dose.

Acetic Acid↗
PubMed2003

The rebound excitation triggered by anticholinergic drugs from ovine pyloric antrum, small bowel and gallbladder.

The effect of anticholinergic drugs on gastrointestinal motility is complex and incompletely recognized. Accordingly, in 6 adult sheep bipolar electrodes and strain gage force transducers were surgically attached to the antral, small intestinal and gallbladder wall at the serosal side. During chronic experiments the myoelectric and mechanical recordings were performed in fasted and non-fasted animals before and after various doses of hexamethonium, atropine and pirenzepine given intravenously. Hexamethonium administration triggered rebound excitation after an inhibitory period almost in all the recording sites. Administration of atropine and pirenzepine evoked these secondary contractions mostly in the small intestine and gallbladder. No rebounds were observed when the anticholinergic drugs were given during feeding. In fasted animals, rebound excitation arrived later but more frequently than in non-fasted animals. The excitatory changes were dose-dependent. In the gallbladder, these values were lower than in the small intestine. The frequency of the recurrent pattern was dependent upon the dose of the anticholinergic drug used. It is concluded that nicotinic receptors are more important than muscarinic receptors in the initiation of the rebound excitation in pyloric antrum while in the small bowel and gallbladder the role of both cholinergic receptors is similar. The anticholinergic drugs should be used with caution in all these clinical situations, where the enhancement of gastrointestinal motility must be avoided.

Animals↗
PubMed1987

On the mechanism of the smooth-muscle action of rosanol.

In vivo and in vitro experiments were performed to clarify some aspects of the mechanism of the smooth-muscle action of rosanol prepared from rose oil. On dogs (in vivo) and on isolated segments from guinea-pig ileum (in vitro) rosanol at high doses exerted a slight inhibitory effect on the activated gastrointestinal motility. The cholinolytic rosanol action proved in in vitro experiments, was found to play an essential role in the mechanism of its gastrointestinal motility-inhibiting effect. The present studies showed a pronounced antagonistic effect of rosanol on the KCl-increased Ca2+ level in rabbit aorta. It might be suggested that this effect of rosanol is also involved in the inhibitory action of rosanol on the activated gastrointestinal motility.

Animals↗
PubMed2004

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. METHODS: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). RESULTS: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. CONCLUSION: Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Abdominal Pain↗
PubMed1995

Effects of KW-5092, a novel gastroprokinetic agent, on intestinal water and electrolyte transport in rats.

KW-5092 ([1-[2-[[[5-(piperidinomethyl)- 2-furanyl]methyl]amino]ethyl]-2-imidazolidinylidene]propanedini trile fumarate) enhances acetylcholine release from enteric neurons and inhibits acetylcholinesterase (AChE), resulting in the enhancement of a wide range of gastrointestinal motilities. The present study examined the effects of KW-5092 on intestinal water and electrolyte transport in rats. In the jejunum, oral or intrajejunal administration of the laxative bisacodyl (30 mg/kg) significantly inhibited absorption of water, Na+ and Cl-, and significantly enhanced K+ secretion. In contrast, neither KW-5092 (1-30 mg/kg) nor the AChE inhibitor neostigmine (0.3-10 mg/kg), orally or intrajejunally administered, affected water or electrolyte transport in the jejunum. Similar results were obtained in the colon when the drugs were applied orally or intracolonically. Moreover, neither KW-5092 (1-30 mg/kg, p.o.) nor neostigmine (0.3-10 mg/kg, p.o.) induced diarrhea, while bisacodyl (30 mg/kg, p.o.) induced diarrhea in all the rats examined. These results demonstrate that KW-5092 or neostigmine at the gastroprokinetic doses does not affect intestinal water or electrolyte transport in rats, suggesting that cholinergic activation enhances gastrointestinal motility rather than intestinal secretion of water and electrolytes.

Animals↗
PubMed1995

Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs.

Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.

Analgesics↗
PubMed1999

Domperidone: a peripherally acting dopamine2-receptor antagonist.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of domperidone in the treatment of gastrointestinal motility disorders and emesis. DATA SOURCES: MEDLINE and Excerpta Medica online databases were searched to identify published reports. STUDY SELECTION: Domperidone has been marketed worldwide outside the US since 1978, and extensive clinical data for this drug are available. This review focuses on the clinical experience from controlled studies of domperidone in the treatment of motility disorders, particularly diabetic gastroparesis. Also, case reports are used in summarizing safety. The control comparator groups included placebo or other prokinetic drugs (metoclopramide and cisapride). Controlled clinical trials of domperidone's efficacy and safety as an antiemetic are also briefly examined. Although a variety of domperidone dosage forms have been marketed, data generated from trials using the 10-mg tablet are highlighted because this is the only dosage form available in Canada and is under investigation in the US. DATA EXTRACTION: Because symptoms do not correlate with objective measures of gastrointestinal motility and they are the primary reason that patients with motility disorders seek treatment, the primary outcome extracted from the clinical studies was symptomatic response to treatment. Safety and efficacy between domperidone and placebo, metoclopramide, or cisapride were compared. DATA SYNTHESIS: Domperidone, a peripheral dopamine2-receptor antagonist, regulates the motility of gastric and small intestinal smooth muscle and has been shown to have some effects on the motor function of the esophagus. It also has antiemetic activity as a result of blockade of dopamine receptors in the chemoreceptor trigger zone. In controlled clinical trials, domperidone provided better relief of symptoms (anorexia, nausea, vomiting, abdominal pain, early satiety, bloating, distension) than placebo in patients with symptoms of diabetic gastropathy; symptomatic improvement was similar with domperidone and metoclopramide or cisapride. Domperidone also provided short-term relief of symptoms in patients with dyspepsia or gastroesophageal reflux, prevented nausea and vomiting associated with emetogenic chemotherapy, and prevented the gastrointestinal and emetic adverse effects of antiparkinsonian drugs. Because very little domperidone crosses the blood-brain barrier, reports of central nervous system adverse effects, such as dystonic reactions, are rare. CONCLUSIONS: Domperidone is a unique gastrokinetic and antiemetic drug. Because of its favorable safety profile, domperidone appears to be an attractive alternative to metoclopramide. In the management of diabetic gastropathy, domperidone's antiemetic activity distinguishes it from cisapride.

Animals↗
PubMed1996

Effects of erythromycin in chronic idiopathic intestinal pseudo-obstruction.

The prokinetic effects of erythromycin, a macrolide antibiotic, on the gastrointestinal tract as a motilin receptor agonist and its potential value for the treatment of gastrointestinal motility disorders have recently attracted interest. The effects of erythromycin on the clinical symptoms and gastrointestinal motility of patients with chronic idiopathic pseudo-obstruction have not been investigated extensively. We presented a case of chronic idiopathic intestinal pseudo-obstruction, in a 67-year-old man in whom oral erythromycin (900 mg/day) dramatically improved postprandial abdominal distention, nausea, and vomiting. Other agents with prokinetic effects on intestinal motility, i.e., cisapride, domperidone, metoclopramide, and trimebutine maleate did not have a favorable effect. Gastric emptying, measured by the sulfamethizole method; and intestinal transit, evaluated using radio-opaque markers, were markedly improved by treatment with erythromycin. Our experience suggests that the prokinetic effects of erythromycin may be of therapeutic value in chronic idiopathic intestinal pseudo-obstruction.

Administration, Oral↗
PubMed2001

Basic pathophysiologic mechanisms in irritable bowel syndrome.

Converging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events.

Animals↗
PubMed1990

Relationship between interdigestive gallbladder emptying, plasma motilin and migrating motor complex in man.

The aim of this study was to elucidate the importance of biliary output for the regulation of migrating motor complex and the release of plasma motilin. Gallbladder emptying was monitored by hepatobiliary scintigraphy, plasma motilin concentration by radioimmunoassay and gastrointestinal motility by a perfused catheter system. During a total recording time of 46 h and 20 min in 16 volunteers, we observed 29 episodes of gallbladder emptying, 27 plasma motilin peaks and 23 activity fronts (phase 3 activity) of the migrating motor complex (MMC). Twelve episodes of gallbladder emptying started in phase 1 and continued into phase 2 of the MMC. The remaining 17 episodes of gallbladder emptying started in phase 2, and three of these continued into phase 3 of the MMC. Biliary output was associated with a significant rise in plasma motilin concentration, whereas plasma motilin significantly decreased after the activity fronts. These observations may explain the well-known fluctuations of plasma motilin concentration in the fasted state. Motilin is released into the circulation as a result of biliary output, while the ensuing activity front of the MMC removes this stimulant from the proximal small bowel, resulting in a fall in plasma motilin. In conclusion, we have confirmed a temporal relationship between biliary output into the duodenum and the release of plasma motilin. The observed transition from phase 1 to phase 2 and from phase 2 to phase 3 of the MMC during gallbladder emptying episodes suggests that biliary output stimulates gastrointestinal motility in the fasted state.

Adolescent↗
PubMed2005

Effect of N-methyl-d-aspartate receptor blockade on neuronal plasticity and gastrointestinal transit delay induced by ischemia/reperfusion in rats.

Intestinal ischemia impairs gastrointestinal motility. The aims of this study were to investigate the effect of intestinal ischemia on gastrointestinal transit and on the expression of enteric transmitters in the rat, and whether the glutamate N-methyl-d-aspartate receptors influence these effects. Ischemia (1 h), induced by occluding the superior mesenteric artery, was followed by 0 or 24 h of reperfusion. Normal and sham-operated rats served as controls. Serosal blood flow was measured with laser Doppler flow meter. Gastrointestinal transit was measured as time of appearance of a marker in fecal pellets. Immunohistochemistry was used to evaluate the number of neurons immunoreactive for neuronal nitric oxide synthase (NOS) or vasoactive intestinal polypeptide and the density of substance P immunoreactive fibers in the myenteric plexus. The N-methyl-d-aspartate receptors antagonist, (+)-5-methyl-10,11-dihydro-5HT-[a,b] cyclohepten-5,10-imine (MK-801) (1 mg/kg i.v.) or the NOS inhibitor, N-nitro-l-arginine (10 mg/kg i.v.) was administered prior to ischemia. Serosal blood flow was decreased by 70% during ischemia, but it was not altered in sham-operated rats. Gastrointestinal transit was significantly prolonged in ischemic/reperfused rats compared with controls. There was a significant increase in the number of vasoactive intestinal polypeptide and neuronal nitric oxide synthase immunoreactive neurons, and a marked decrease of substance P immunoreactive fibers in ischemia followed by 24 h of reperfusion animals compared with controls. These alterations were not observed in ischemia without reperfusion. A significant delay of gastrointestinal transit and increase of vasoactive intestinal polypeptide neurons were also observed in sham-operated rats. The changes in transmitter expression and gastrointestinal transit in ischemic/reperfused rats were prevented by pre-treatment with the NOS inhibitor, N-nitro-l-arginine or the N-methyl-d-aspartate receptors antagonist, MK-801. This study suggests an involvement of the glutamatergic system and its interaction with nitric oxide in intestinal ischemia/reperfusion. Ischemia/reperfusion might induce local release of glutamate that activates N-methyl-d-aspartate receptors leading to increased production of nitric oxide and adaptive changes in enteric transmitters that might contribute to gastrointestinal dysmotility.

Analysis of Variance↗