Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health

Chial, Heather J.; Camilleri, Michael; Burton, Duane; Thomforde, George M.; Olden, Kevin W.; Stephens, Debra

doi:10.1152/ajpgi.00266.2002

Cited by 110 publications

(94 citation statements)

References 32 publications

(47 reference statements)

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“…The SSRI paroxetine enhanced gastric accommodation in humans although it did not alter fasting gastric tone (44). Another study reported a marked enhancing effect of Venalfaxine-XR, a SNRI, on gastric accommodation (7). Because impaired accommodation is associated with early satiety and weight loss and is one of the contributing factors of functional dyspepsia (46), DVS may not be appropriate for patients with functional dyspepsia.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Dai¹,

Lei²,

Chen

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, serotonin-norepinephrine reuptake inhibitor. Antidepressants have been widely used for the treatment of functional gastrointestinal disorders. Possible roles of DVS on gastrointestinal motility have not been studied. The aim of this study was to investigate the effects of DVS on gastric slow waves (GSW), antral contractions, and gastric accommodation in dogs. Fifteen healthy dogs implanted with gastric serosal electrodes and a gastric cannula were studied in four separate sessions: control, DVS (50 mg), propranolol (1 mg·kg Ϫ1 ·h Ϫ1 ), and propranolol ϩ DVS. GSW were measured via the gastric serosal electrodes. Antral contractions were assessed via an intraluminal manometric catheter inserted via the gastric cannula. The sympathovagal activity was assessed from the spectral analysis of the heart rate variability signal. Gastric tone was measured by barostat via an intragastric balloon inserted into the fundus via the gastric cannula. In the postprandial period, in comparison with the control, DVS reduced the percentage of normal GSW (P ϭ 0.001) and increased the percentage of tachygastria (P ϭ 0.005) and bradygastria (P ϭ 0.002). Simultaneously, DVS increased the sympathetic activity (P ϭ 0.006) and the sympathovagal ratio (low frequency/high frequency; P ϭ 0.044). These effects were blocked by propranolol. DVS attenuated postprandial antral contractions and gastric accommodation. The postprandial antral contractile index (area under the curve) was decreased by 26% with DVS (P ϭ 0.013), and gastric accommodation was decreased by about 50% with DVS (P Ͻ 0.001). The inhibitory effect of DVS on gastric accommodation was blocked by propranolol. DVS inhibits gastric contractions, slow waves, and accommodation in the fed state. These inhibitory effects are associated with an increased sympathetic modulation in the gastrointestinal system. Cautions should be made when DVS is used for treating patients with depression and gastric motility disorders. desvenlafaxine succinate; antidepressants; gastrointestinal motility ANTIDEPRESSANTS ARE WIDELY used for the treatment of functional gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome (17,20,55). The rationale for the use of antidepressants in functional gastrointestinal disorders is based on the following potential effects. First, antidepressants may improve psychiatric and psychological symptoms, particularly anxiety and depression (11,18,47). Second, antidepressants have central analgesic actions and alter central processing of visceral pain stimuli (10, 27). Third, antidepressants may have local pharmacological actions on the gut and modulate gut sensorimotor functions (3,8,9).Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, the third serotonin-norepinephrine reuptake inhibitor (SNRI) approved by the U.S. Food and Drug Administration for the treatment of major depressive disorders in 2008 (26, 35). It is a novel salt form of the isolated major active metab...

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Section: Discussionmentioning

confidence: 99%

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Dai¹,

Lei²,

Chen

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Each distension was maintained for 1 min with an interstimulus interval of 2 min during which the balloon was deflated to BOP. This approach has been shown to be reliable in multiple previous studies (4,14,15,45) because the intensity ratings are generally proportional to the magnitude of the distension pressures. Study participants were blinded to the distension order, which was provided by the study Fig.…”

Section: Rectal Compliance and Sensation By Barostatmentioning

confidence: 99%

“…Serotonergic and noradrenergic systems interact to modulate pain perception in the spinal cord and brain peripherally and to activate the hypothalamo-pituitary-adrenal axis (32). In humans, a combination of serotonin and norepinephrine reuptake inhibition has a more profound effect on human gastric and colonic sensory and motor functions relative to selective serotonin reuptake (14,15). These and other data suggest that serotonergic and adrenergic mechanisms may interact to alter gastrointestinal motor and sensory functions, and these may involve G protein transduction.…”

mentioning

confidence: 91%

Candidate genes and sensory functions in health and irritable bowel syndrome

Camilleri

Busciglio

Carlson

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Zinsmeister AR. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 295: 219 -225, 2008. First published May 29, 2008 doi:10.1152/ajpgi.90202.2008.-Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including ␣2A (C-1291G), ␣2C (Del 332-325), GN␤3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GN␤3 was associated only with fasting GV; we did not detect associations between ␣2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GN␤3 with fasting GV may explain, in part, the reported association of GN␤3 with dyspepsia. adrenergic; serotonergic; GN␤3; SLC6A4; G protein; receptor ADRENERGIC MECHANISMS alter gastrointestinal reflexes involved in intestinal propulsion, coordinated motor activity in the small bowel and colon, and gastrointestinal tone and fluid secretion (12,46). Norepinephrine is also involved in control of pain including supraspinal inhibition of pain, e.g., due to a change in the behavioral state (37) including stress, which contributes to gut motility disorders (10).Among ␣2 receptors, the ␣2A subtype appears to be critically important for control of motor functions, such as gastrointestinal transit in mice (40) and colonic circular smooth muscle in canine colon (47). The ␣2 receptor agonist, clonidine, inhibits gastric and colonic tone, phasic contractility, and sensation in the rectum and colon in response to balloon distension in healthy humans (4, 43).Serotonergic (5-HT) mechanisms also alter gut absorptive, motor, and sensory functions via actions in the gut, spinal cord, and brain stem (27). Ligand-receptor interaction results in c...

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“…This makes them an attractive option for the treatment of those with IBS-D, particularly, in those where pain is a predominant feature. In contrast, the SSRI, paroxetine, has been shown to accelerate gut transit time (101). SSRIs generally have a lower side effect profile than TCAs and should be considered in the treatment of IBS when psychological symptoms or coexistent somatic pain syndromes are present, or in those patients who have not responded to laxatives or antispasmodics.…”

Section: Anti-depressantsmentioning

confidence: 99%

Irritable bowel syndrome; update on pathophysiology and management

Quigley¹,

Craig²

2012

Turk J Gastroenterol

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The functional gastrointestinal disorders (FGID) are symptom-based disorders that cannot be currently explained by definable structural or biochemical causes (1). These disorders are common: the presence of at least one functional GI disorder was identified in 70% of participants in a large US householder survey (2). An associated co-morbid psychiatric condition such as anxiety, mood or panic disorder is seen in up to 60% of those attending gastroenterology outpatient clinics with a functional compliant (3). Functional GI disorders are associated with significant impairment of quality of

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Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health

Cited by 110 publications

References 32 publications

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Candidate genes and sensory functions in health and irritable bowel syndrome

Irritable bowel syndrome; update on pathophysiology and management

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