No abstract available.
Alprostadil ; Gastrointestinal Motility ; Lubiprostone

Abdominal bloating is a very common and troublesome symptom of all ages, but it has not been fully understood to date. Bloating is usually associated with functional gastrointestinal disorders or organic diseases, but it may also appear alone. The pathophysiology of bloating remains ambiguous, although some evidences support the potential mechanisms, including gut hypersensitivity, impaired gas handling, altered gut microbiota, and abnormal abdominal-phrenic reflexes. Owing to the insufficient understanding of these mechanisms, the available therapeutic options are limited. However, medical treatment with some prokinetics, rifaximin, lubiprostone and linaclotide could be considered in the treatment of bloating. In addition, dietary intervention is important in relieving symptom in patients with bloating.
Alprostadil ; Gastrointestinal Diseases ; Humans ; Hypersensitivity ; Metagenome ; Peptides ; Reflex ; Rifamycins ; Lubiprostone

Chronic constipation is one of the most common digestive diseases frequently observed in a clinical setting. It has been known to cause considerable damage to the quality of life of patients. Despite recent developments, there are considerable limitations in the use of constipation-modulating agents in Korea. Chloride channel inhibitors, such as lubiprostone and linaclotide, have not been introduced in Korea yet, and prucalopride and several kinds of polyethylene glycol are not covered under medical insurance. This article assesses medicines that are clinically available for the management of constipation in Korea, with a brief review of agents that have recently developed around the world.
Chloride Channels ; Constipation* ; Drug Therapy* ; Humans ; Insurance ; Korea ; Lubiprostone ; Polyethylene Glycols ; Quality of Life

Irritable bowel syndrome with constipation and chronic functional constipation are common digestive disorders that negatively impact quality of life and account for billions of dollars in health care costs. Related to the heterogeneity of pathogenesis that underlie these disorders and the failure of symptoms to reliably predict underlying pathophysiology, traditional therapies provide relief to only a subset of affected individuals. The evidence surrounding new and emerging pharmacologic treatments, which include both luminally and systemically acting drugs, is discussed here. These include agents such as lubiprostone, bile acid modulations, guanylate cyclase-C receptor agonists, serotonin receptor modulators and herbal therapies.
Bile ; Constipation* ; Health Care Costs ; Irritable Bowel Syndrome* ; Laxatives ; Population Characteristics ; Quality of Life ; Serotonin Receptor Agonists ; Lubiprostone

A significant proportion of chronic constipation patients are dissatisfied with their treatment. Recently, a number of new medications have been introduced for patients refractory to conventional laxatives, such as prucalopride, lubiprostone, linaclotide, and elobixibat. Prucalopride is a novel gastrointestinal prokinetic agent that acts as a 5-hydroxytryptamine type 4 (5-HT4) agonist. Compared with older nonselective 5-HT4 agonists, the higher selectivity of prucalopride for 5-HT4 receptors can reduce the risk of significant adverse cardiovascular events. Prucalopride improves stool frequency and consistency, and reduces the need for rescue medications. Lubiprostone, a chloride channel activator, increases the secretion of intestinal fluid, improves the stool frequency and consistency, and reduces straining. Linaclotide, a guanylate cyclase-C agonist, is effective in treating patients with chronic constipation and its effect on visceral sensitivity, as shown mainly in animal studies, provides an attractive pharmaceutical option for patients with irritable bowel syndrome with constipation. Elobixibat is an ileal sodium-dependent bile acid transporter inhibitor that blocks the enterohepatic circulation of bile acids, increasing the bile acid concentration in the intestine, which accelerates colonic transit and softens the stool. A phase III trial of the treatment of chronic constipation and irritable bowel syndrome with constipation is underway. The clinical application of new-generation laxatives will contribute to the management of chronic constipation refractory to conventional laxatives.
Animals ; Bile ; Bile Acids and Salts ; Chloride Channels ; Colon ; Constipation ; Enterohepatic Circulation ; Humans ; Intestines ; Irritable Bowel Syndrome ; Laxatives* ; Receptors, Serotonin, 5-HT4 ; Serotonin ; Serotonin 5-HT4 Receptor Agonists ; Lubiprostone

Lubiprostone is a chloride (Cl-) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K+] channel blocker) and apamin (a calcium [Ca2+]-dependent K+ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K+ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K+ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K+ channel through a prostanoid EP receptor-independent mechanism.
Alprostadil ; Animals ; Apamin ; Calcium ; Colon* ; Constipation ; Glyburide ; Interstitial Cells of Cajal* ; Membranes ; Mice* ; Muscle, Smooth ; Nitric Oxide ; Patch-Clamp Techniques ; Pinacidil ; Potassium ; Tetraethylammonium ; Lubiprostone

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patient's most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain.
Abdominal Pain ; Acupuncture ; Alprostadil ; Anti-Bacterial Agents ; Antidepressive Agents ; Carbolines ; Complementary Therapies ; Constipation ; Diarrhea ; Flatulence ; Gastrointestinal Diseases ; Humans ; Hypersensitivity ; Inflammation ; Irritable Bowel Syndrome ; Metagenome ; Parasympatholytics ; Placebos ; Probiotics ; Rifamycins ; Serotonin ; Biomarkers ; Lubiprostone

BACKGROUND/AIMS: Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone. METHODS: Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) +/- EP1 antagonist. Significance was established using Student t test and P < 0.05. RESULTS: Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 +/- 0.88 to 4.43 +/- 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 +/- 0.70 vs. 4.43 +/- 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 +/- 0.01 to 1.97 +/- 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. CONCLUSIONS: In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.
Alprostadil ; Animals ; Baths ; Chloride Channels ; Constipation ; Contracts ; Dinoprostone ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Intestinal Secretions ; Intestine, Small ; Isotonic Solutions ; Mice ; Muscle Tonus ; Muscle, Smooth ; Muscles ; Pylorus ; Receptors, Prostaglandin E ; Receptors, Prostaglandin E, EP1 Subtype ; Lubiprostone