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Thread: Gut motility

  1. #1

    Gut motility

    seneca, here is the reference that I found on pharmacological drugs that affect intestinal motility and sphincters:

    • Scarpignato C and Pelosini I (1999). Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. Can J Gastroenterol 13 Suppl A:50A-65A. Summary: Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect. Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Nantes, France.

    [This message was edited by Wise Young on 04-30-03 at 02:34 AM.]

  2. #2
    • Camilleri M (1999). Motor function in irritable bowel syndrome. Can J Gastroenterol 13 Suppl A:8A-11A. Summary: The evidence supporting a role of abnormal motor function in irritable bowel syndrome (IBS) is reviewed. Symptoms commonly present in IBS patients, such as vomiting, diarrhea, constipation or incomplete rectal evacuation, indicate that a motor disorder is implicit as either a primary or secondary disturbance. Physiological studies implicate a disturbance of transit through the small bowel and proximal colon, and abnormal motor responses of the rectum to distention in IBS patients. Intestinal contractions (physiological or 'abnormal') are associated with the sensation of pain, suggesting that these contractions are interactions between abnormal motor and sensory functions in IBS. Therapies aimed at correcting abnormal transit or antispasmodics are the main pharmacological approaches to the relief of IBS, and, although the latter are not always effective in the long term response to treatment, they support the role of dysmotility in IBS. Most novel therapies under trial probably modulate both sensory and motor functions, and are discussed briefly. In summary, the weight of clinical, physiological and pharmacological evidence supports a role of abnormal motility in IBS. Mayo Clinic and Mayo Foundation, Rochester, USA.

  3. #3
    Thanks Dr. Young.

    For more on antispasmodic/anticholinergic agents, please click below.

  4. #4
    Bumping for chat roomer.

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