Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities

Niang, Le Yu; Heckroth, Matthew; Mathur, Prateek; Abell, Thomas L.

doi:10.1080/13543784.2023.2186222

Cited by 4 publications

(2 citation statements)

References 142 publications

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“…The results demonstrate that both domperidone and metoclopramide effectively relieved symptoms of diabetic gastroparesis and improved gastric emptying rates. Symptom relief, as indicated by the reduction in symptom scores, was notably significant in both groups, with a slightly greater reduction observed in the domperidone group (52% vs. 45%) (8). This finding aligns with the peripheral action of domperidone, emphasising its potential advantages in symptom management (9).…”

Section: Discussionsupporting

confidence: 56%

Domperidone vs Metoclopramide: Comparative Evaluation of Efficacy in Treating Diabetic Gastroparesis

NAWAZ,

SHAH,

AHMED

et al. 2024

Biol Clin Sci Res J

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Diabetic gastroparesis, a common complication of diabetes mellitus, presents a challenging clinical scenario characterised by delayed gastric emptying and symptoms such as nausea, vomiting, abdominal pain, and bloating. Objectives: The primary aim of the study is to compare domperidone vs metoclopramide to evaluate their efficacy in treating diabetic gastroparesis. Methods: This comparative study was conducted in DHQ Hospital Nowshera Khyber Pakhtunkhwa—from June 2022 to June 2023. Data was collected from 190 patients from both genders. Patients meeting the inclusion criteria are randomised into Group A (Domperidone) and Group B (Metoclopramide). The severity of gastroparesis symptoms is assessed using validated symptom-scoring tools before treatment initiation and at regular intervals throughout the study. Results: Data was collected from 190 patients suffering from DM. The mean age of the patients in group A was 52.4 ± 8.2 years and in group B, 53.1 ± 7.5 years. There were 105 female and 185 male patients. The mean duration of DM is 12.3 ± 4.1 years and 11.8 ± 3.8 years in groups A and B, respectively. Group A (Domperidone) and Group B (Metoclopramide) demonstrated significant improvement in symptom scores from baseline to the final assessment. Group A exhibited a substantial reduction in symptom score from 18.2 ± 4.5 at baseline to 8.7 ± 3.2 at the end of the study (p < 0.001), while Group B showed a decrease from 17.9 ± 4.3 to 9.5 ± 3.8 (p < 0.001). Moreover, both groups experienced notable reductions in gastric emptying time. Conclusion: It is concluded that both domperidone and metoclopramide are effective in managing diabetic gastroparesis, with nuances in their safety profiles.

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Section: Discussionsupporting

confidence: 56%

Domperidone vs Metoclopramide: Comparative Evaluation of Efficacy in Treating Diabetic Gastroparesis

NAWAZ,

SHAH,

AHMED

et al. 2024

Biol Clin Sci Res J

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“…75 The most useful current drugs are dopamine blockers and NK-1 antagonists, although many other compounds are being studied. 76 For patients with drug-refractory gastroparesis, consideration of pyloric therapies, gastric bioelectric devices, and enteric tubes are options. For symptomatic patients with gastroparesis, current recommendations include neurologic, neuromuscular, and autonomic evaluation.…”

Section: Full-thickness Biopsies In Gastroparesis Syndromesmentioning

confidence: 99%

Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders

Naing,

Mathur,

Chhabra

et al. 2023

Semin Neurol

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Gastroparesis syndromes (GpS) are a spectrum of disorders presenting with characteristic symptoms increasingly recognized as being gastrointestinal (GI) neuromuscular disorders (NMDs). This review focuses on GpS as a manifestation of neurologic disorders of GI NMD. GpS can be associated with systemic abnormalities, including inflammatory, metabolic, and serologic disorders, as well as autoimmune antibodies via nerve and muscle targets in the GI tract, which can be treated with immunotherapy, such as intravenous immunoglobulin. GpS are associated with autonomic (ANS) and enteric (ENS) dysfunction. Disorders of ANS may interact with the ENS and are the subject of continued investigation. ENS disorders have been recognized for a century but have only recently begun to be fully quantified. Anatomic structural changes in the GI tract are increasingly recognized in GpS. Detailed descriptions of anatomic changes in GpS, and their correlation with physiologic findings, have opened a new era of investigation. The management of GpS, when viewed as GI NMD, has shifted the paradigms of both diagnosis and treatment. This article concludes with current approaches to GpS directed at underlying neuromuscular pathology.

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Characterization of neuromuscular transmission and projections of muscle motor neurons in the rat stomach

Di Natale,

Hunne,

Stebbing

et al. 2024

American Journal of Physiology-Gastrointestinal and Liver Physi

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The stomach is the primary reservoir of the gastrointestinal tract, where ingested content is broken down into small particles. Coordinated relaxation and contraction is essential for rhythmic motility and digestion, but how the muscle motor innervation is organized to provide appropriate graded regional control is not established. In this study, we recorded neuromuscular transmission to the circular muscle using intracellular microelectrodes to investigate the spread of influence of intrinsic motor neurons. In addition, microanatomical investigations of neuronal projections and pharmacological analysis were conducted to investigate neuromuscular relationships. We found that inhibitory neurotransmission to the circular muscle is graded with stimulus strength and circumferential distance from the stimulation site. The influence of inhibitory neurons declined between 1 and 11 mm from the stimulation site. In the antrum, corpus and fundus the declines at 11 mm were about 20%, 30%, and 50% respectively. Stimulation of inhibitory neurons elicited biphasic hyperpolarizing potentials often followed by prolonged depolarizing events in the distal stomach, but only hyperpolarizing events in the proximal stomach. Excitatory neurotransmission influence varied greatly between proximal stomach, where depolarizing events occurred, and distal stomach, where no direct electrical effects in the muscle were observed. Structural studies utilizing microlesion surgeries confirmed a dominant circumferential projection. We conclude that motor neuron influences extend around the gastric circumference, that the effectiveness can be graded by the recruitment of different numbers of motor neuron nerve terminals to finely control gastric motility, and that the ways in which the neurons influence the muscle differ between anatomical regions.

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Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities

Cited by 4 publications

References 142 publications

Domperidone vs Metoclopramide: Comparative Evaluation of Efficacy in Treating Diabetic Gastroparesis

Domperidone vs Metoclopramide: Comparative Evaluation of Efficacy in Treating Diabetic Gastroparesis

Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders

Characterization of neuromuscular transmission and projections of muscle motor neurons in the rat stomach

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