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)

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.
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PMID:Role of antispasmodics in the treatment of irritable bowel syndrome. 2487 26

We evaluated the effect of SKI3246, the 50% ethanol extract of the rhizome of Atractylodes japonica, on visceral hypersensitivity, which is a major characteristic feature of IBS. We used various rat models of visceral hypersensitivity to assess the visceral pain responses to colorectal distension (CRD) in comparison with conventional IBS treatments. Oral administration of SKI3246 dose-dependently and significantly attenuated the abdominal withdrawal reflex (AWR) score in a model of acetic acid-induced visceral hypersensitivity. We also found that it reduced the number of abdominal contractions in response to CRD in a model of 2,4,6-trinitrobenzenesulfonic acid-induced visceral hypersensitivity, which was comparable to ramosetron or alosetron. Furthermore, treatment with SKI3246 also increased the pain threshold and abolished the elevated AWR scores to CRD in a rat model of neonatal maternal separation. We presumed that the modulation of the NK2 receptor is involved in the inhibitory activity of SKI3246 on the basis that it significantly inhibited the contraction of the distal colonic muscle induced by neurokinin A, the NK2 receptor agonist. The present results indicate that SKI3246 has the potential to be an effective therapeutic agent for IBS, especially insofar as it can relieve visceral hypersensitivity.
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PMID:Inhibitory effects of SKI3246, the rhizome extract of Atractylodes japonica, on visceral hypersensitivity in experimental irritable bowel syndrome rat models. 2507 Jul 63

5-Hydroxytryptamine (5-HT) released from colonic mucosal enterochromaffin (EC) cells is a major signaling molecule, which participates in the pathophysiological regulation of colonic functions in gut disorder including irritable bowel syndrome (IBS), but the endogenous modulator system for the 5-HT release is not yet well elucidated. Our in vitro studies in guinea-pig colon have indicated that the cascade pathway of neuronal tachykinergic NK3 receptors and NK2 receptors on peptide YY (PYY)-containing endocrine L cells represents an endogenous modulator system for 5-HT release from EC cells and that melatonin, endogenous tachykinins and PYY play important roles in modulation of the release of 5-HT from EC cells via the endogenous NK2/NK3 receptor cascade system. This review aims at examining the potential role of the endogenous tachykinergic NK2/NK3 receptor cascade system controlling the release of 5-HT from EC cells, with special attention being paid to the pathophysiology of gut disorders including IBS.
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PMID:An Endogenous Tachykinergic NK2/NK3 Receptor Cascade System Controlling the Release of Serotonin from Colonic Mucosa. 2663 Sep 61

Tachykinins act as neurotransmitters and neuromodulators in the central and peripheral nervous system. Preclinical studies and clinical trials showed that inhibition of the tachykinin receptors, mainly NK2 may constitute a novel attractive option in the treatment of irritable bowel syndrome (IBS). In this review, we focused on the role of tachykinins in physiology and pathophysiology of gastrointestinal (GI) tract. Moreover, we summed up recent data on tachykinin receptor antagonists in the therapy of IBS. Ibodutant is a novel drug with an interesting pharmacological profile, which exerted efficacy in women with diarrhea-predominant IBS (IBS-D) in phase II clinical trials. The promising results were not replicable and confirmed in phase III of clinical trials. Ibodutant is not ready to be introduced in the pharmaceutical market and further studies on alternative NK2 antagonist are needed to make NK2 antagonists useful tools in IBS-D treatment.
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PMID:The place of tachykinin NK2 receptor antagonists in the treatment diarrhea-predominant irritable bowel syndrome. 3101 19


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