Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome

Gorard, Stephen; Libby, G. W.; Farthing, M. J. G.

doi:10.1111/j.1365-2036.1994.tb00273.x

Cited by 182 publications

(103 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, selective serotonin re-uptake inhibitors (SSRIs) prevent the re-uptake of serotonin alone. Serotonin acts as a secretagogue, and tends to stimulate GI motility [Gorard et al 1994]. Accordingly, SSRIs could particularly help those with constipation-predominant IBS (IBS-C).…”

Section: Antidepressantsmentioning

confidence: 99%

“…At the molecular level, TCADs inhibit the re-uptake of both serotonin and norepinephrine, increasing the bioavailability of these neurotransmitters in the synaptic cleft. They also antagonize muscarinic acetylcholine receptors [Gillman, 2007], These antimuscarinic effects of TCADs are responsible for many of their side effects, including constipation, dry mouth, and blurred vision [Gorard et al 1994]. However, slowing of GI transit may be of therapeutic advantage in diarrhea-predominant IBS (IBS-D) [Drossman et al 2003].…”

Section: Antidepressantsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents

Sainsbury

Ford

2010

Therap Adv Gastroenterol

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract of unknown etiology. The diagnosis of IBS is made clinically, using symptom-based criteria such as the Manning or Rome criteria. Medical therapy for this condition has traditionally been directed towards symptom relief, using fiber or antispasmodic agents. In recent years, emerging data have confirmed the efficacy of antidepressants, psychological therapies, 5-HT 3 antagonists, 5-HT 4 agonists, and probiotics in the short-term treatment of IBS, although whether these therapies influence the long-term course of the disease is unknown. Increasing knowledge regarding the pathophysiological mechanisms underlying IBS has resulted in a number of novel molecular treatments, which show promise. These include therapies targeting gastrointestinal mucosal chloride channels and guanylate cyclase-C receptors, as well as highly selective agents influencing serotonergic transmission that, at the time of writing, do not appear to have any severe deleterious effects. In this article we provide a summary of current and emerging therapies in this field.

show abstract

Section: Antidepressantsmentioning

confidence: 99%

Section: Antidepressantsmentioning

confidence: 99%

Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents

Sainsbury

Ford

2010

Therap Adv Gastroenterol

View full text Add to dashboard Cite

show abstract

“…Their mechanism in IBS is not completely understood, but has been postulated to relate to an ability to modulate central and peripheral pain perception [110,111] , improve underlying psychiatric conditions, and possibly improve gut motility through modification of neurotransmitter activity [112,113] . Unfortunately, randomized-controlled trials to date have largely been hindered by poor study design and methodological flaws, making it difficult to judge the therapeutic value of these agents [114][115][116] .…”

Section: Antidepressantsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

show abstract

“…Furthermore, abnormal expression of SERT in the central nervous system may contribute to a number of complex behavioral traits and disorders (1, 35, 38). 5-HT released by enterochromaffin cells is sequestered into mucosal epithelial cells (7,36) and changes in SERT function can lead to changes in gastrointestinal (GI) function as evidenced by the GI side effects associated with 5-HT-selective reuptake inhibitors (10,11,32). Also, transgenic mice lacking SERT frequently exhibit diarrhea associated with watery stools interspersed with periods of constipation (5).…”

mentioning

confidence: 99%

IFN-γ and TNF-α decrease serotonin transporter function and expression in Caco2 cells

Foley¹,

Pantano²,

Ciolino³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Foley KF, Pantano C, Ciolino A, Mawe GM. IFN-␥ and TNF-␣ decrease serotonin transporter function and expression in Caco2 cells. Am J Physiol Gastrointest Liver Physiol 292: G779 -G784, 2007. First published December 14, 2006; doi:10.1152/ajpgi.00470.2006.-Recent studies have shown that mucosal serotonin (5-HT) transporter (SERT) expression is decreased in animal models of colitis, as well as in the colonic mucosa of humans with ulcerative colitis and irritable bowel syndrome. Altered SERT function or expression may underlie the altered motility, secretion, and sensation seen in these inflammatory gut disorders. In an effort to elucidate possible mediators of SERT downregulation, we treated cultured colonic epithelial cells (Caco2) with conditioned medium from activated human lymphocytes. Application of the conditioned medium caused a decrease in fluoxetine-sensitive [3 H]5-HT uptake. Individual proinflammatory agents were then tested for their ability to affect uptake. Cells were treated for 48 or 72 h with PGE2 (10 M), IFN-␥ (500 ng/ml), TNF-␣ (50 ng/ml), IL-12 (50 ng/ml), or the nitric oxide-releasing agent S-nitrosoglutathione (GSNO; 100 M).[ 3 H]5-HT uptake was then measured. Neither PGE nor IL-12 had any effect on [ 3 H]5-HT uptake, and GSNO increased uptake. However, after 3-day incubation, both TNF-␣ and IFN-␥ elicited significant decreases in SERT function. Neither TNF-␣ nor IFN-␥ were cytotoxic when used for this period of time and at these concentrations. These two cytokines also induced decreases in SERT mRNA and protein levels. By altering SERT expression, TNF-␣ and IFN-␥ could contribute to the altered motility and expression seen in vivo in ulcerative colitis or irritable bowel syndrome.SERT; tumor necrosis factor; interferon; colitis; inflammatory bowel disease; inflammation SEROTONIN (5-hydroxytryptamine; 5-HT) is the main monoamine signaling molecule in the gut, where it acts as a paracrine neurotransmitter (9, 25). Specialized enteroendocrine cells, enterochromaffin cells, release 5-HT into the lamina propria of the intestines, where it activates receptors located on processes of intrinsic and extrinsic primary afferent neurons. This leads to activation of local motor and secretory reflexes and the transduction of sensory signals to the brain stem and spinal cord. A critical aspect of paracrine and neurotransmitter signaling is the termination of transmission by degradation or removal of the signaling molecule. In the case of 5-HT, this involves rapid clearance of 5-HT from the intercellular space by the 5-HT reuptake transporter (SERT), which is expressed by mucosal epithelial cells (7,21,36).SERT is a member of the highly conserved Na ϩ /Cl Ϫ -dependent transporter gene family containing 12 transmembrane domains (2). Transporters for 5-HT and other monoamines are of particular interest because they are sites of action for most clinically efficacious antidepressants, as well as for psychoactive drugs of abuse such as amphetamines, cocaine, and MDMA (ecstasy). Furthermore, abnormal expression o...

show abstract

Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome

Cited by 182 publications

References 34 publications

Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents

Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents

Updates on treatment of irritable bowel syndrome

IFN-γ and TNF-α decrease serotonin transporter function and expression in Caco2 cells

Contact Info

Product

Resources

About