In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.

01 May 2014·European Journal of PharmacologyQ3 · MEDICINE

Inhibitory effect of the selective serotonin 5-HT3 receptor antagonist ramosetron on duodenal acidification-induced gastric hypersensitivity in rats

Q3 · MEDICINE

Article

Author: Nakata-Fukuda, Mari ; Keto, Yoshihiro ; Yamano, Mayumi ; Uchiyama, Yasuo ; Yokoyama, Toshihide ; Hirata, Takuya

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are both functional gastrointestinal disorders and frequently co-occur in patients. While one cause of FD appears to be gastric hypersensitivity, whether the hypersensitivity is affected by IBS treatments remains unclear, given the lack of appropriate animal models for testing. Here, we established an experimental model of duodenal acidification-induced gastric hypersensitivity in conscious rats. The model involved duodenal acidification induced by the infusion of hydrochloric acid into the proximal duodenum, with the nociceptive response being determined as the change in mean arterial pressure (MAP) during gastric distension via an indwelling latex balloon. Using our model we evaluated the effects of duodenal acidification, increased distension pressure, and orally administered therapeutic agents for IBS with diarrhea (IBS-D). Duodenal acidification enhanced the pressor response during gastric distension, and pretreatment with the opioid κ-receptor agonist fedotozine (10mg/kg, intra-arterial) inhibited the pressor response. Pressure levels of 15-60 mm Hg increased MAP in response to gastric distension. The serotonin 5-HT3 receptor antagonist ramosetron (30 μg/kg) inhibited MAP increase induced by duodenal acidification, with no other IBS-D therapeutic agents showing any effect. In contrast, the serotonin 5-HT3 receptor agonist m-chlorophenylbiguanide (1mg/kg) significantly enhanced the pressor response during gastric distension. These findings indicate that the serotonin 5-HT3 receptor plays a key role in duodenal acidification-induced gastric hypersensitivity in rats, suggesting that ramosetron may reduce FD symptoms by ameliorating sensitized gastric perception.

01 Feb 2008·Current Treatment Options in Gastroenterology

Opioid-induced bowel dysfunction

Article

Author: Howard Y. Chang ; Anthony J. Lembo

OPINION STATEMENTOpioid analgesics are commonly prescribed for moderate to severe pain. Opioids exert effects via receptors in the central and enteric nervous systems. Thus, central opioid analgesia can be limited by side effects involving the gastrointestinal tract, particularly by gastrointestinal motility delay. Opioid-induced bowel dysfunction is commonly treated with bulking agents, stimulant laxatives, lubiprostone, and tegaserod (removed from the market in March 2007). However, these treatments' efficacy in opioid bowel dysfunction has not been proven. Recent research has focused on developing peripheral μ opioid antagonists such as methylnatrexone and alvimopan. These drugs selectively block μ opioid receptors in the enteric nervous system without penetrating the blood-brain barrier and can avert adverse gastrointestinal symptoms of opioids without reducing central analgesia. Methylnaltrexone and alvimopan also reduce hospitalization duration in surgical patients with postoperative ileus. A second line of research has focused on peripheral κ opioid agonists that modulate nociception in the enteric nervous system without producing central nervous system side effects. Asimadoline and fedotozine reduce nociceptive reflexes caused by gut distention and improve pain symptoms in patients with irritable bowel syndrome. ADL 10-0101 (Adolor Corp., Exton, PA) is another peripheral κ opioid agonist that lowers pain scores in patients with chronic pancreatitis. Although peripheral κ opioid agonists are promising, clinical studies are needed to assess their efficacy in treating opioid-induced bowel dysfunction.

100 Deals associated with Fedotozine tartrate

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Irritable Bowel Syndrome	NDA/BLA	IT	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	CA	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	CA	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	NL	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	NL	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	CH	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	FR	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	CH	Pfizer Inc.	-
Irritable Bowel Syndrome	NDA/BLA	FR	Pfizer Inc.	-
Irritable Bowel Syndrome	Phase 2	IT	Pfizer Inc.	-

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