Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudo-obstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonic motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation.
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PMID:Prokinetic agents for lower gastrointestinal motility disorders. 813 79

Naloxone acts as an opioid antagonist, displacing opioid drugs from cellular receptors. Among opioid substances, beta-endorphins are able to bind to several cell receptors, even including those expressed by immune cells. In this respect, evidence has been provided that in the course of viral infections, as well as in patients with ulcerative colitis high levels of beta-endorphins are detectable. Here, peripheral blood lymphocytes (PBL) from 21 HCV infected patients and 14 patients with IBD, respectively, were incubated with Naloxone and Naloxone + Ca2+ in order to evaluate a putative modulation of PBL-mediated antibacterial activity. In fact, previous studies have demonstrated a reduction of this T-cell activity in HCV and IBD patients. In general terms, the above treatment led to a recovery of the depressed antibacterial activity. In some cases, increase in T lymphocyte function was obtained with Naloxone alone, while in other cases the combination Naloxone + Ca2+ gave rise to a restorative effect. Of note, in some instances, lymphocytes were unresponsive to pharmacological modulation. The overall results suggest that beta-endorphins may down modulate T-cell antibacterial response in HCV and in IBD patients by saturating peripheral receptors on immune cells. Therefore, it is likely that Naloxone and/or Naloxone + Ca2+ may displace opioid drugs, thus antagonizing their effects.
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PMID:In vitro effects of naloxone on T-lymphocyte-dependent antibacterial activity in hepatitis C virus (HCV) infected patients and in inflammatory bowel disease (IBD) patients. 1132 42

Abnormal rectal motor physiology and visceral hypersensitivity are implicated in the pathogenesis of irritable bowel syndrome. Endogenous opioids are involved in both the regulation of gut motility and the processing of sensory information. Our aim was to study the effect of suppression of endogenous opioid function by naloxone on rectal sensorimotor function in health. Eighteen healthy subjects participated in a rectal barostat study. Sensorimotor function was evaluated during two consecutive stepwise distensions separated by 30 min of basal tone recording, and with perception scoring on a 0-6 graded scale. Naloxone was administered, after 15 min of basal tone measurements, as an intravenous bolus (0.4 mg), followed by continuous infusion (20 microg kg(-1) h(-1)) in a placebo-controlled, single-blinded and randomized fashion. Naloxone did not alter rectal sensitivity. Comparison of visual analogue scale scores between naloxone and saline did not reveal altered intensities of pain or discomfort. Compared to the baseline distension, a significant adaptive increase in compliance occurred during the second distension after saline (7.8 +/- 0.7 vs 11.0 +/- 0.6 mL mmHg(-1), P = 0.0016). This dynamic change in rectal compliance did not occur after naloxone administration (8.8 +/- 0.7 vs 10.1 +/- 0.8 mL mmHg(-1), ns). Low intensity tonic distension induced a rectal adaptive relaxation, which was absent after naloxone. Naloxone does not alter rectal sensitivity but abolishes rectal adaptation in response to repeated balloon distention. These observations suggest that the endogenous opioid system is involved in control of rectal tone rather than rectal sensitivity.
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PMID:Influence of naloxone on rectal sensorimotor function in health. 1922 64