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PubMed1987

Pharmacological profile of PD 117302, a selective kappa-opioid agonist.

1 PD 117302, a new nonpeptide opioid compound shown in in vitro studies to be a selective kappa-opioid agonist, has been evaluated in vivo for antinociceptive activity and other effects characteristic of kappa-receptor activation. 2 Dose-related long lasting antinociception was produced by PD 117302 against a mechanical noxious stimulus in rats following intravenous, subcutaneous or oral administration. 3 PD 117302 was effective in raising the nociceptive threshold to mechanical and chemical but not to thermal noxious stimuli in the mouse. This effect was attenuated in animals pretreated with the opioid antagonist naloxone. 4 In addition to producing antinociception, PD 117302 also caused naloxone-reversible locomotor impairment and diuresis, effects that are typical of kappa-agonists. 5 PD 117302 did not cause respiratory depression, inhibition of gastrointestinal motility or naloxone-precipatated withdrawal jumping in mice, effects that are associated with actions at the mu-opioid receptor. 6 The pharmacological profile of PD 117302 in vivo is consistent with in vitro data suggesting that PD 117302 is a selective agonist at the kappa-opioid receptor.

Analgesics↗
PubMedDate not supplied

[Nitric oxide (NO)--Nobel prize in medicine and physiology for 1998].

On October 12, 1998. The Nobel Assembly announced the award of the Nobel Prize in Medicine and Physiology to pharmacologists Robert Furchgott, Louis Ignarro, and Ferid Murad. The Nobel Committee decided to award the prize for their discoveries concerning--nitric oxide as a signalling molecule in the cardiovascular system. Nitric oxide (NO) has a key importance for vascular tonus, acts as a signal molecule in the nervous system and plays an important function in the immunological system. Nitric oxide is a multifunction molecule which controls the blood pressure, modulates gastrointestinal motility. It is produced in abnormal level intensifies septic shock and destruction of nervous tissue. NO is important in different branches of medicine. For instance NO gas has been used to reduced high blood pressure in the lung of infants. Several unknown NO applications in medicine are waiting for discovery.

Animals↗
PubMed1985

Interaction studies and other investigations of the pharmacology of propofol ('Diprivan').

The anaesthetic properties of propofol ('Diprivan') have been described previously. This report summarizes additional studies designed to investigate some aspects of the general pharmacology of propofol. Following recovery from anaesthesia with propofol there was no evidence of any central anticholinergic or anticonvulsant effect in mice. An anti-convulsant effect followed thiopentone anaesthesia. In mice anaesthetized with propofol 24 h after the last of 4 daily doses of phenelzine, amitriptyline, diazepam or alcohol, no marked potentiation of anaesthesia was found. Pretreatment with alcohol on the day of anaesthesia potentiated thiopentone but not propofol anaesthesia. Oral doses of propofol up to 300 mg/kg failed to induce anaesthesia in mice. The acute administration of the beta-adrenoceptor antagonists, atenolol or propranolol was well tolerated during anaesthesia with propofol in pigs. In the cat the arrhythmia threshold to adrenaline was greater than that in cats anaesthetized with halothane and no ganglion blocking or alpha-adrenoceptor antagonist properties were demonstrated. No potent or specific agonist or antagonist properties were detected in the range of in vitro systems examined. Neither propofol nor thiopentone had any effect on ADP-induced platelet aggregation or whole blood clotting time. Bronchomotor tone and gastrointestinal motility were unaffected by propofol. Tests of renal function indicated only a slight reduction in sodium excretion, similar to that seen with thiopentone. A normal corticosterone response to ACTH was seen in rats anaesthetized for 90 min with an infusion of propofol.

Adrenergic beta-Antagonists↗
PubMed1979

VMH obesity reduced but not reversed by scopolamine methyl nitrate.

Chronic administration of scopolamine methyl nitrate, at doses much greater than required to block vagally mediated insulin secretion, reduced static phase VMH obesity by only 31%. At least 59% of the obesity persisted even when the initially effective dose (0.15 mg/Kg, 4 times/day) was increased eight-fold. The larger dose also did not prevent VMH hyperphagia and weight gain when scopolamine treatment was begun before the lesion. By ten days after the lesion, reduced gastrointestinal motility apparently prevented further weight gain. These results suggest that much of the obesity caused by VMH lesions is independent of vagally mediated insulin secretion or other excess vagal efferent activity. The doses used in this experiment were large in order to provide strong evidence for this conclusion.

Animals↗
PubMed2001

Review article: erythromycin as a prokinetic agent in infants and children.

Erythromycin has been used as an antibiotic for more than four decades, but only in the last 10 years have other therapeutic benefits of this agent been exploited. Animal and human studies have demonstrated a prokinetic effect on the gastrointestinal tract at sub-antimicrobial doses (typically a quarter or less of the antibiotic dose). A limited number of studies have been performed in children to investigate this action. A review of this literature is particularly pertinent given the frequency of clinical problems related to gastrointestinal dysmotility in children and the limited availability of prokinetic agents in paediatric practice, compounded by the recent withdrawal of cisapride. The prokinetic effects of erythromycin have been investigated in infants with dysmotility associated with prematurity, in low birth-weight infants recovering from abdominal surgery, and in older children with a variety of other gastrointestinal disorders. Only one randomized placebo-controlled trial has been conducted. All except one of these studies have shown a beneficial effect of erythromycin in either promoting tolerance of enteral feeds or enhancing a measured index of gastrointestinal motility. Erythromycin appears to be equally effective when given orally (as ethylsuccinate or estolate) or intravenously (as lactobionate). Significantly, no serious adverse effects have been reported in studies in which erythromycin has been used for its prokinetic effects, although fatal reactions have followed the intravenous administration of erythromycin to neonates in antibiotic doses.

Administration, Oral↗
PubMed2003

[Abdominal complaints and neurological symptoms as an early sign of lung cancer: a manifestation of the anti-Hu syndrome].

In two patients, women aged 73 and 46 years, gastrointestinal symptoms were initially not recognised as a paraneoplastic syndrome due to small-cell lung cancer. This led to redundant diagnostics as well as a delay in final diagnosis. The anti-Hu syndrome is characterised by the presence of anti-Hu antibodies and neurological symptoms. About a quarter of the patients with the anti-Hu syndrome will develop gastrointestinal motility disorders in the course of their illness. The primary tumour is usually a small-cell lung cancer. Whereas the presence of anti-Hu antibodies appears to be beneficial for the oncological prognosis, the neurological outcome is less favourable.

Aged↗
PubMed2002

[Psychophysiology of visceral pain].

This paper reviews the most important research strategies in the context of the psychophysiology of visceral pain. These are disturbed gastrointestinal motility, visceral hypersensitivity and central nervous system mechanisms such as response bias, attentional bias and affective evaluation. The most prominent research methods and results are reviewed and methodological problems are discussed. From a psychophysiological perspective, visceral pain remains a complex and heterogeneous syndrome in which stress and coping may be etiologically as important as pathophysiological mechanisms of peripheral origin and central nervous system mechanisms like attentional bias.

Central Nervous System↗
PubMed2005

[Small intestinal bacterial overgrowth. An update].

Small intestinal bacterial overgrowth (SIBO) is characterized by nutrient malabsorption, associated with an excessive number of bacteria in the proximal small intestine. Unfortunately, the diagnosis of bacterial overgrowth presents several difficulties and limitations, and as yet there is not a widespread agreement on the best diagnostic test. SIBO occurs when there are alterations in intestinal anatomy, gastrointestinal motility, or a lack of gastric acid secretion. The true association between SIBO and irritable bowel syndrome and celiac disease remains uncertain. The treatment usually consists in the eradication of bacterial overgrowth with repeated courses of antimicrobials, nutritional support and when it is possible, the correction of underlying predisposing conditions.

Anti-Bacterial Agents↗
PubMedDate not supplied

On the physiology of GIP and GLP-1.

Recent studies have indicated that GIP and GLP-1 are about as important as each other in the incretin effect, being released rapidly after meals and being active already at fasting glucose levels. Although the density of GLP-1 producing cells is higher distally, GlP-1 is normally secreted by jejunal L-cells, explaining the rapid onset of secretion. Moreover, many endocrine cells in the small intestine appear to produce both GIP and GLP-1. Both are metabolized rapidly by the dipeptidyl peptidase IV enzyme, but unlike GIP, about 90 % of GLP-1 is degraded before it reaches the systemic circulation. Apparently, before it is degraded, GLP-1 activates sensory afferents in the gastrointestinal mucosa with cell bodies in the nodose ganglion, signaling onwards to the brain stem and the hypothalamus. A similar mechanism seems to be involved in GLP-1's effect on gastrointestinal motility and secretion, and perhaps its actions on appetite and food intake, all of which may be even more physiologically important than its effects on the beta cells. Cardiovascular and neuroprotective actions of GLP-1 have also recently been reported. Regarding GIP, several lines of evidence suggest that GIP, in addition to its incretin effects, may affect lipid metabolism and promote lipid storage.

Animals↗
PubMed1986

Pharmacology of the novel H2 antagonist famotidine: in vitro studies.

The novel antiulcer drug famotidine was found to be a potent and selective inhibitor of histamine H2 receptors. Its activity on different parameters involving H2 receptors was higher than that of other compounds of the family: pA2 values were 8.33, 7.86 and 7.83 in the guinea pig atria, guinea pig papillary muscle and isolated rat gastric secretion, respectively. Apart from quantitative differences, famotidine differed from the other compounds, since it caused a competitive antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The duration of the inhibitory action on the "in vitro" gastric secretion resembled that of cimetidine and ranitidine. Famotidine was highly effective (approximately 10 times as potent as ranitidine) also on the rat uterus (unsurmountable antagonism) and on the guinea pig gallbladder (pA2 value = 7.71). Famotidine was apparently devoid of non-specific effects concerning the gastrointestinal motility even at very high concentrations (10(-4) M). In this respect, famotidine appeared to be more selective than cimetidine and ranitidine at the H2 receptor level. The high potency, the peculiarity of the antagonism and the lack of side-effects on a number of isolated preparations, indicate this H2 antagonist as a very peculiar member of the group.

Animals↗
PubMedDate not supplied

Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract.

Functional disorders of the gastrointestinal tract comprise a common but ill-defined group of diseases; they primarily afflict women. Although predominantly involving nerve and muscle, the cellular and molecular bases of the pathogenesis of these functional disorders are unknown. Clinical studies indicate that some result from neural dysfunction within the enteric nervous system, others may be due to muscular problems, and the causes of still others remain unknown. Laboratory studies have shown that ovarian products such as progesterone, luteinizing hormone, human chorionic gonadotropin, and relaxin (but not estrogen), are neural antagonists of gastrointestinal motility. The production and secretion of these ovarian substances are controlled by gonadotropin-releasing hormone (GnRH) released from the hypothalamus; they probably act on gamma-aminobutyric acid receptors and alter chloride influx into the cell. GnRH analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal axis and inhibit the secretion of gonadal products involved in such hormone-dependent diseases as endometriosis and prostate cancer. Acting on the GnRH receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH analogs are also effective neural modulators in such disorders as functional bowel disease. These analogs are a promising new group of compounds that may be used to treat difficult gastrointestinal problems.

Chorionic Gonadotropin↗
PubMed1996

Influence of cisapride on the pharmacokinetics and antihypertensive effect of sustained-release nifedipine.

To investigate the clinical significance of interactions between cisapride and sustained-release nifedipine, we compared the plasma nifedipine concentration and blood pressure after administration of nifedipine alone (20 mg) with those obtained after administration of nifedipine cisapride (2.5 mg) in 20 patients with hypertension. The plasma nifedipine level was not altered by cisapride at one hour after administration, but was significantly increased at two (p < 0.01), three (p < 0.01), and four (p < 0.05) hours when compared with the level measured after nifedipine alone. Cisapride significantly decreased the mean blood pressure at three hours (p < 0.05) after administration of nifedipine. The acetaminophen method was used to determine gastric emptying time. The plasma concentration of acetaminophen at 45 minutes after administration was significantly increased by cisapride, suggesting that enhanced gastrointestinal motility might be the basis for the increase in the plasma nifedipine concentration. These results suggest that enhancement of the antihypertensive effect of nifedipine can occur when the drug is prescribed with cisapride, and that caution is needed when using such a combination therapy.

Aged↗
PubMed2004

[Effect of mold fungus spore consumption with food on systemic anaphylaxis in rats].

An influence was studied in experiment of intragastrically administrated milk cream contaminated with mould fungi spores on systemic anaphylactic reaction gravity in Wistar albino rats sensitized with egg albumin (EA). During 28 days sensitized rats intragastrically received cream containing 10(3) or 10(6) colony forming units of 5 fungal species in one cm3. After being challenged rats developed mild anaphylactic shock followed by elevation of small intestinal permeability for macromolecular tracer polyethylene glycol 4000. An increase of small intestinal permeability was also noticed in unsensitized rats that were fed with cream contaminated with 10(6) spores per cm3. Unexpectedly these effects were not additive: the intestinal permeability in sensitized rats decreased at maximal level of contamination. This may be explained by strengthening of gastrointestinal motility in these animals. Significant elevation of antibody production against EA was revealed in sensitized rats that received cream contaminated by spores at high level. The data obtained signify that milk products fungal contamination that could not be revealed by sense may nevertheless have negative impact on intestinal barrier function and sensitization.

Anaphylaxis↗
PubMed1987

Clinical pharmacology of famotidine: a summary.

Famotidine is a competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect in humans is inhibition of gastric acid secretion. Dose-related suppression of basal and stimulated (meal, pentagastrin) gastric acid output has been shown with oral doses of 5-40 mg. The 40 mg dose is associated with the highest inhibitory effect, the longest duration of action, and the greatest response uniformity. After oral administration, antisecretory activity begins within 1 h, reaches a maximum in 1-3 h, and lasts 10-12 h. In addition to the earlier onset of effect, intravenous famotidine is about twice as potent as oral, a result consistent with a systemic bioavailability of oral famotidine of about 43%. Studies in patients and in healthy volunteers have shown that famotidine does not affect cardiovascular, renal, endocrine, pancreatic exocrine, or gastrointestinal motility functions. Oral famotidine is incompletely absorbed, reaching peak plasma concentrations in 1-3 h. It is eliminated primarily through the kidneys (about 70%), mostly as the parent compound. Its average elimination half-life in healthy subjects is 2.8 h. Half-life is prolonged nonlinearly in patients with decreased renal function. To date, clinically important interactions with other drugs have not been described for famotidine.

Drug Interactions↗
PubMed1997

Role of central interleukin-1 beta in gastrointestinal motor disturbances induced by lipopolysaccharide in sheep.

Cytokines are involved in the symptoms of the acute phase response induced by infectious diseases in humans as well as in animals, and interleukin-1 beta (IL-1 beta) has a pivotal role in these changes. The role of central IL-1 beta in the gastrointestinal hypomotility and fever evoked by intravenous administration of lipopolysaccharide (LPS) and the mechanisms involved, were investigated in sheep as an experimental model. LPS (0.1 microgram/kg, intravenously) induced gastrointestinal hypomotility and fever that were significantly reduced by prior intracerebroventricular administration of IL-1 receptor antagonist protein (IL-1ra, 2 micrograms/kg). The effects of LPS were mimicked by intracerebroventricular IL-1 beta (50 ng/kg), whereas IL-1 beta injected intravenously at the same dose only caused a slight and transient fever without modifying the gastrointestinal motility. Prior intracerebroventricular administration of the cyclooxygenase inhibitor indomethacin (100 micrograms/kg) but not the corticotropin-releasing factor (CRF) receptor antagonist alpha-helical CRF9-41 (5 micrograms/kg) blocked all effects by both LPS and IL-1 beta. These results suggest that in sheep, LPS induces digestive motor disturbances through a central release of IL-1 beta and prostaglandins.

Animals↗
PubMed2006

Myoelectric activity and motility of the Roux limb after cut or uncut Roux-en-Y gastrojejunostomy.

AIM: To explore the mechanisms of uncut Roux-en-Y gastrojejunostomy, which is used to decrease the occurrence of Roux stasis syndrome. METHODS: The changes of myoelectric activity, mechanic motility and interstitial cells of Cajal (ICC) of the Roux limb after cut or uncut Roux-en-Y gastrojejunostomy were observed. RESULTS: When compared with the cut group, the amplitude (1.15 +/- 0.15 mV vs 0.48 +/- 0.06 mV, P < 0.05) and frequency (14.4 +/- 1.9 cpm vs 9.5 +/- 1.1 cpm, P < 0.01) of slow waves and the incidence (98.2% +/- 10.4% vs 56.6% +/- 6.4%, P < 0.05) and amplitude (0.58 +/- 0.08 mV vs 0.23 +/- 0.06 mV, P < 0.01) of spike potential of the Roux limb in the uncut group were significantly higher. The migrating myoelectric complexes (MMC) phase III duration in the uncut group was significantly prolonged (6.5 +/- 1.1 min vs 4.4 +/- 0.8 min, P < 0.05), while the MMC cycle obviously shortened (42.5 +/- 6.8 vs 55.3 +/- 8.2 min, P < 0.05). Both gastric emptying rate (65.5% +/- 7.9% vs 49.3% +/- 6.8%, P < 0.01) and intestinal impelling ratio (53.4% +/- 7.4% vs 32.2% +/- 5.4%, P < 0.01) in the uncut group were significantly increased. The contractile force index of the isolated jejunal segment in the uncut group was significantly higher (36.8 +/- 5.1 vs 15.3 +/- 2.2, P < 0.01), and the expression of c-kit mRNA was significantly increased in the uncut group (0.82 +/- 0.11 vs 0.35 +/- 0.06, P < 0.01). CONCLUSION: Uncut Roux-en-Y gastrojejunostomy may lessen the effects of operation on myoelectric activity such as slow waves, spike potential, and MMC, decrease the impairment of gastrointestinal motility, and remarkably increase the expression of c-kit mRNA.

Anastomosis, Roux-en-Y↗
PubMed2004

Nonantimicrobial effects of antibacterial agents.

One of the major advances in modern medicine was the development of antimicrobial chemotherapy. However, many antibacterial agents have unexpected or undesirable nonantimicrobial effects on humans. Microbes and man share many essentials of life, including DNA, adenosine triphosphate, and other biochemical pathways. Hence, some of these nonantimicrobial effects may also turn out to be pharmacologically useful. Oral hypoglycemic agents (i.e., sulfonylureas) and a certain diuretic agent (acetazolamide) are derivatives of sulfonamides. Erythromycin has been used clinically for its stimulatory effect on gastrointestinal motility. Macrolides, lincosamides, and tetracyclines have been known for their immunomodulatory effects. A tetracycline has been used to treat the syndrome of inappropriate antidiuretic hormone. Aminoglycosides may influence mucus production in patients with cystic fibrosis. Other antimicrobials may have side effects that are not therapeutically useful, such as osmotic diuresis with high-dose beta -lactam administration, neuromuscular blockade of aminoglycosides, dysglycemia of fluoroquinolones, and serotonin syndrome with oxazolidinones.

Anti-Bacterial Agents↗
PubMed2005

The role of gender and biological sex in irritable bowel syndrome.

Irritable bowel syndrome (IBS), which is characterized by abdominal pain or discomfort that is associated with altered bowel function (diarrhea, constipation, or alteration between the two), is one of several gastrointestinal motility disorders. IBS affects up to one in five North Americans, mostly women. The reason(s) this disorder is reported more often by women than men, and the role of gender and biological sex in the prevalence, pathophysiology, symptom presentation, impact on quality of life, diagnosis, and response to treatment, are poorly understood. The purpose of this article is to review the evidence surrounding the roles of gender and biological sex in IBS.

Female↗