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

Compound F-461, 3-diethylamino-2,2-dimethylpropyl 5-(p-nitrophenyl)-2-furoate hydrochloride, was evaluated pharmacologically and was found to exert non-anticholinergic smooth muscle spasmolytic activity along the gastrointestinal tract of animals. F-461 was additionally discovered to inhibit gastric acid secretion and to prevent cold + restraint stress-induced ulcers. Local anesthesia, both surface and infiltration, was also elicited by F-461. The pharmacologic properties of F-461, as revealed in this study, are indicative of potential usefulness of this drug in the therapy of spastic colon and/or peptic ulcers.
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PMID:F-461, 3-diethylamino-2,2-dimethylpropyl 5-(p-nitrophenyl)-2-furoate hydrochloride, a new non-anticholinergic spasmolytic and gastric acid inhibitor. 98 68

Ondansetron (GR 38032F), a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, is a highly effective and safe drug for the prophylaxis and treatment of emesis induced by various chemotherapy regimens in cancer patients. Recent studies have shown that ondansetron is also effective in post-anaesthesia and radiation-induced nausea and vomiting. When compared with high-dose metoclopramide, ondansetron appeared to be superior. Furthermore, ondansetron has been shown to improve stool consistency and to reduce stool frequency in patients with diarrhoea-predominant irritable bowel syndrome.
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PMID:Closing remarks. Ondansetron: effects on gastrointestinal motility. 183 38

In some emergency situations of colo-rectal pathology, especially those characterized by hemorrhaging, the endoscopy has acquired, with the passing of years, a fundamental role both from the diagnostic and the therapeutic point of view. In no more than 25% of the lower intestinal tract hemorrhages, the clinical picture does have the signs of an emergency. The diverticula, IBD and angiodysplasias are primarily responsible for rendering these characteristics. Even when possible problems concerning an accurate intestinal cleaning can arise, a correct diagnosis is possible at least in seven cases out ten. When the colonoscopy isn't conclusive and the bleeding persists may be recommended the selective arteriography (helpful also in hemorrhages lower than 0.5 ml/min). Also in cases of acute obstructive syndrome the colonoscopy, taking advantage of the direct view of the lesion, can give a correct diagnosis, sometimes supported by the histologic examination. Regarding the operating capacity of the method, the endoscopy can resolve minute and localized bleeding lesions. The Argon or Nd:YAG laser photocoagulation is widely used. Recently BICAP and heater probe methods have been developed, which aveld the problem connected to the HF electrocoagulation. A very efficacious and simple method is that of injecting 1:10.000 adrenalin, 1% polidocanol, absolute ethanol or hypertonic solution around the lesion. The scarred strictures are those more easily and safely treated by pneumatic dilatation or (limited to the rectum-sigmoid) by Savary sounds. In the volvulus or bowel invagination, just by having the endoscope goes up in the lumen, often normal condition settles again. In the Ogilvie's syndrome you can deflate the cecum with an aspirator or more simply by positioning a tube above the hepatic flexure, with 85% success. In the malignant strictures the debulking of tumor mass by laser treatment, sometimes followed by dilatation, may be preparatory to the surgery or purely palliative. Finally the extraction of foreign bodies must be performed, in order to obtain a relaxed anal sphincter, in general anaesthesia or by a previous rigid rectoscope dilatation.
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PMID:[Emergencies in colorectal diseases: role of the endoscopist]. 892 30

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

It has been suggested that serotonin (5-hydroxytryptamine) type-4 (5-HT4) receptors modulate the sensitivity of intrinsic afferents of the intestinal mucosa. We studied the involvement of 5-HT4receptors in the modulation of extrinsic afferent sensitivity of the intestinal wall. During distension ramps, mechanoreceptive rectal afferents in sacral dorsal roots were examined in decerebrate anaesthesia-free cats using the selective 5-HT4receptor partial agonist, tegaserod (HTF 919), and the 5-HT4receptor antagonist, SB 203186. The static discharge rate of the afferents evoked by rectal distension decreased after intravenous (i.v.) administration of tegaserod at intraluminal pressures above 30 mmHg, with the most effective reduction occurring at 50 mmHg. The effect was dose-dependent, with maximal reduction occurring at 1.2 mg kg-1 bodyweight, and could be partly reversed by i.v. administration of SB 203186. Tegaserod did not alter the pressure-volume relationship (compliance) of the rectum. It is tentatively concluded that 5-HT4receptor activation has an inhibitory effect on intramural mechanoreceptors in the cat's rectum. Our results are in line with the observation that tegaserod relieves the sensory symptoms of patients suffering from irritable bowel syndrome.
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PMID:Serotonin type-4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum. 1206 5

Spinal cord stimulation (SCS) has been found to relieve neuropathic and ischemic pain clinically and to attenuate a nociceptive reflex in an animal model of acute colonic hypersensitivity. The goal of the present study was to determine the effect of SCS in a rat model of post-inflammatory colonic hypersensitivity. Acute inflammation was induced in rats by a single enema of trinitrobenzenesulfonic acid (TNBS) (50 mg/kg, 0.5 ml, 25% EtOH). Control rats received a single saline enema. A visceromotor behavioral response (VMR), induced by innocuous colorectal distention (30 mm Hg, 10 min) was used to quantify the level of colonic sensitivity on day 3 and 30 post-enema. Prior to VMR testing, under general anesthesia, an electrode (cathode) was placed epidurally on the dorsal surface of the spinal cord at L1 with a paravertebral anode plate. Three to 7 days after implantation of the SCS electrode, the effect of SCS (50 Hz, 0.2 ms, amplitude 90% of motor threshold for 30 min) on colonic sensitivity was determined. On day 30, rats that had received a single TNBS enema were hypersensitive to innocuous colonic distention when compared to rats that received a saline enema (VMR/10 min: TNBS: 17.2+/-0.8 vs. Saline: 9.6+/-1.1, p<0.01). Spinal cord stimulation significantly reduced the VMR in the TNBS-enema group to a value that resembled the saline-enema group (VMR/10 min: TNBS: 11.2+/-1.2 vs. Saline: 10.0+/-1.0). This study provides the first evidence that SCS might be a potential therapeutic for the treatment of abdominal pain observed in patients with post-inflammatory irritable bowel syndrome.
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PMID:Spinal cord stimulation attenuates visceromotor reflexes in a rat model of post-inflammatory colonic hypersensitivity. 1618 12

Irritable bowel syndrome and interstitial cystitis frequently overlap. We have shown that acute colitis sensitizes urinary bladder afferents to both mechanical and chemical stimuli and that chronic colitis similarly produces neurogenic cystitis. We hypothesize that chronic irritation of the colon releases neuropeptides from bladder afferents, leading to receptor sensitization and neurogenic inflammation. Female Sprague-Dawley rats received intrarectal trinitrobenzenesulfonic acid (TNBS) or vehicle 3 days following either systemic capsaicin (CP) pretreatment or vehicle. Ten days later, action potentials of single-unit pelvic C-fiber afferents with receptive fields in the bladder were recorded under urethane anesthesia during graded bladder distensions (UBD) or intravesical capsaicin (vCP) administration. In controls, UBD increased bladder afferent firing in proportion to intravesical pressure. At intravesical pressures of 30 mmHg and above, the percent increase in afferent firing was significantly accentuated following TNBS compared with controls (1,222 +/- 176 vs. 624 +/- 54%, P < 0.01). The response to vCP was also enhanced (4,126 +/- 775 vs. 1,979 +/- 438%, P < 0.01). Systemic depletion of neuropeptides from sensory nerves abolished these effects. Histological examination of the bladders revealed an increase in mast cell density in TNBS-treated animals compared with controls (18.02 +/- 1.25 vs. 3.11 +/- 0.27 mast cells/x100 field, P < 0.01). This effect was significantly ameliorated with CP (10.25 +/- 0.95, P < 0.5 vs. TNBS-treated animals). In summary, chronic colonic irritation in the rat sensitizes urinary bladder afferents to noxious stimuli and causes mast cell infiltration in the bladder. Depletion of neuropeptides from sensory afferents diminishes these effects, suggesting they play an important role.
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PMID:Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. 1692 45

5-HT3 receptors are members of the Cys-loop superfamily of ligand-gated ion channels. In both the central and the peripheral nervous systems, 5-HT3 receptors excite postsynaptic cells and modulate the release of neurotransmitters from presynaptic neurons. 5-HT3 receptors are known to be involved in mediation of nausea/emesis caused by chemo/radio-therapy and anaesthesia, and more recently have also been found to be involved in irritable bowel syndrome. 5-HT3 receptors have also been suggested to play a role in a range of other indications, including various psychiatric disorders. This review summarizes the current evidence for the contribution of 5-HT3 subunit genes to disease phenotypes arising from association studies. Furthermore, it suggests how in vitro characterization of naturally occurring genetic variants can be used to obtain a better understanding of the causal relationship between gene and disease.
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PMID:Do polymorphisms in the human 5-HT3 genes contribute to pathological phenotypes? 1705 18

Limbic associated pelvic pain is a proposed pathophysiology designed to explain features commonly encountered in patients with chronic pelvic pain, including the presence of multiple pain diagnoses, the frequency of previous abuse, the minimal or discordant pathologic changes of the involved organs, the paradoxical effectiveness of many treatments, and the recurrent nature of the condition. These conditions include endometriosis, interstitial cystitis, irritable bowel syndrome, levator ani syndrome, pelvic floor tension myalgia, vulvar vestibulitis, and vulvodynia. The hypothesis is based on recent improvements in the understanding of pain processing pathways in the central nervous system, and in particular the role of limbic structures, especially the anterior cingulate cortex, hippocampus and amygdala, in chronic and affective pain perception. Limbic associated pelvic pain is hypothesized to occur in patients with chronic pelvic pain out of proportion to any demonstrable pathology (hyperalgesia), and with more than one demonstrable pain generator (allodynia), and who are susceptible to development of the syndrome. This most likely occurs as a result of childhood sexual abuse but may include other painful pelvic events or stressors, which lead to limbic dysfunction. This limbic dysfunction is manifest both as an increased sensitivity to pain afferents from pelvic organs, and as an abnormal efferent innervation of pelvic musculature, both visceral and somatic. The pelvic musculature undergoes tonic contraction as a result of limbic efferent stimulation, which produces the minimal changes found on pathological examination, and generates a further sensation of pain. The pain afferents from these pelvic organs then follow the medial pain pathway back to the sensitized, hypervigilant limbic system. Chronic stimulation of the limbic system by pelvic pain afferents again produces an efferent contraction of the pelvic muscles, thus perpetuating the cycle. This cycle is susceptible to disruption through blocking afferent signals from pelvic organs, either through anesthesia or muscle manipulation. Disruption of limbic perception with psychiatric medication similarly produces relief. Without a full disruption of both the central hypervigilance and pelvic organ dysfunction, pain recurs. To prevent recurrence, clinicians will need to include some form of therapy, either medical or cognitive, targeted at the underlying limbic hypervigilance. Further research into novel, limbic targeted therapies can hopefully be stimulated by explicitly stating the role of the limbic system in chronic pain. This hypothesis provides a framework for clinicians to rationally approach some of the most challenging patients in medicine, and can potentially improve outcomes by including management of limbic dysfunction in their treatment.
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PMID:Limbic associated pelvic pain: a hypothesis to explain the diagnostic relationships and features of patients with chronic pelvic pain. 1729 60

Activation of the vagal afferents by noxious gastrointestinal stimuli suggests that vagal afferents may play a complex role in visceral pain processes. The contribution of the vagus nerve to visceral pain remains unresolved. Previous studies reported that patients following chronic vagotomy have lower pain thresholds. The patient with irritable bowel syndrome has been shown alteration of vagal function. We hypothesize that vagal afferent nerves modulate visceral pain. Visceromotor responses (VMR) to graded colorectal distension (CRD) were recorded from the abdominal muscles in conscious rats. Chronic subdiaphragmatic vagus nerve sections induced 470, 106, 51, and 54% increases in VMR to CRD at 20, 40, 60 and 80 mmHg, respectively. Similarly, at light level of anesthesia, topical application of lidocaine to the subdiaphragmatic vagus nerve in rats increased VMR to CRD. Vagal afferent neuronal responses to low or high-intensity electrical vagal stimulation (EVS) of vagal afferent Adelta or C fibers were distinguished by calculating their conduction velocity. Low-intensity EVS of Adelta fibers (40 microA, 20 Hz, 0.5 ms for 30 s) reduced VMR to CRD at 40, 60, and 80 mmHg by 41, 52, and 58%, respectively. In contrast, high-intensity EVS of C fibers (400 microA, 1 Hz, 0.5 ms for 30 s) had no effect on VMR to CRD. In conclusion, we demonstrated that vagal afferent nerves modulate visceral pain. Low-intensity EVS that activates vagal afferent Adelta fibers reduced visceral pain. Thus EVS may potentially have a role in the treatment of chronic visceral pain.
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PMID:Subdiaphragmatic vagal afferent nerves modulate visceral pain. 1842 Aug 25


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