The effect of levosulpiride on <i>in vitro</i> motor patterns in the human gastric fundus, antrum, and jejunum

Gallego, Diana; Ortega, Omar; Arenas, Cristina Núñez de; López‐Lerma, Ingrid; Mans, E.; Clavé, Père

doi:10.1111/nmo.12788

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…These were the only RCTs to report consistently that patients had to have failed other therapies to be eligible for inclusion, although we believe that patients with refractory symptoms would be less likely to be recruited into trials of drugs used first‐line for FD, such as PPIs or H 2 RAs. This is in keeping with the literature for the management of other functional gastrointestinal disorders, where central neuromodulators have effects on gastrointestinal motility and function via actions on peripheral dopamine, noradrenaline and serotonin receptors, 100‐102 such as irritable bowel syndrome 103,104 . This suggests that earlier use of these drugs may be beneficial, and that large head‐to‐head studies of TCAs vs conventional therapies, such as PPIs, are required in primary care.…”

Section: Discussionsupporting

confidence: 78%

Systematic review and network meta‐analysis: efficacy of drugs for functional dyspepsia

Ford

Martin

Black

et al. 2020

Aliment Pharmacol Ther

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Summary Background Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown. Aim To perform a systematic review with network meta‐analysis to resolve this uncertainty. Methods We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. Results We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58‐0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36‐0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo. Conclusions TCAs, histamine‐2 receptor antagonists, standard‐ and low‐dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.

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Section: Discussionsupporting

confidence: 78%

Systematic review and network meta‐analysis: efficacy of drugs for functional dyspepsia

Ford

Martin

Black

et al. 2020

Aliment Pharmacol Ther

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“…Finally, levosulpiride, a prokinetic 5HT 4 agonist/D 2 antagonist, can be used to improve gastric emptying in patients with dyspepsia and diabetic or idiopathic Gp. Due to dopamine antagonism, prolactin can be stimulated by levosulpiride and cause galactorrhea and menstrual irregularities in women [79] .…”

Section: Prokineticsmentioning

confidence: 99%

Gastroparesis: New insights into an old disease

Usai-Satta¹,

Bellini²,

Morelli³

et al. 2020

WJG

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The primary aim of World Journal of Gastroenterology (WJG, World J Gastroenterol) is to provide scholars and readers from various fields of gastroenterology and hepatology with a platform to publish high-quality basic and clinical research articles and communicate their research findings online.WJG mainly publishes articles reporting research results and findings obtained in the field of gastroenterology and hepatology and covering a wide range of topics including gastroenterology, hepatology, gastrointestinal endoscopy, gastrointestinal surgery, gastrointestinal oncology, and pediatric gastroenterology.

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“…The convincing basic science and the observed effects of cisapride prompted the development of several other agents with more specific binding to the 5-HT 4 receptor. Activation of this pathway facilitates acetylcholine release, which modifies intrinsic signaling and could potentially improve motor function and maintain physiologically relevant patterns 98 . While conceptually appealing and backed by strong preclinical studies, the track record of these agents is littered with problems.…”

Section: Treatment Of Hypomotilitymentioning

confidence: 99%

Disorders of gastrointestinal hypomotility

2016

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Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.

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The effect of levosulpiride on in vitro motor patterns in the human gastric fundus, antrum, and jejunum

Abstract: Our results suggest that the prokinetic effects of levosulpiride in humans are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.

Cited by 7 publications

References 39 publications

Systematic review and network meta‐analysis: efficacy of drugs for functional dyspepsia

Systematic review and network meta‐analysis: efficacy of drugs for functional dyspepsia

Gastroparesis: New insights into an old disease

Disorders of gastrointestinal hypomotility

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