Journal of Neurogastroenterology and Motility : eISSN 2093-0887 / pISSN 2093-0879

Table. 1.

Summary of Pathophysiology-directed Therapeutic Approach for Disorders for Gut-Brain Interactions

Drug name Function/pathway Pathophysiological mechanisms Clinical outcome DGBI types
Prokinetics Prucalopride 5-HT4R agonist Altered gut motility Improved GI symptoms as assessed by the GCSI. Gastroparesis, FD, chronic constipation
Improved solid gastric emptying.
Felcisetrag Selective 5-HT4R agonist Altered gut motility Accelerated transit of solids throughout the gut in patients with idiopathic or diabetic gastroparesis. Gastroparesis
Stimulate motility and secretion through enhanced release of acetylcholine from excitatory motor neurons and interneurons.
Alosetron 5-HT3R antagonist Altered gut motility Improved stool consistency and bowel movements. IBS-D
Buspirone 5-HT1R agonist Altered gut motility Fundus relaxation, improve gastric accommodation. FD
Relamorelin Ghrelin receptor agonist Altered gut motility Stimulates nodose afferents and DMV neurons and accelerates gastric emptying. Gastroparesis
Metoclopramide Dopamine-2 receptor antagonists Altered gut motility Improved gut motility. FD, gastroparesis
Acotiamide Muscarinic receptor antagonists Altered gut motility Inhibits acetylcholinesterase and antagonizes the presynaptic muscarinic receptors, present on cholinergic nerve endings, which leads to an increase in acetylcholine levels in the synaptic cleft. FD
Antibiotics Neomycin Modulating gut microbiota profile Gut microbiota dysbiosis Shifting the microbial community composition. IBS
Rifaximin Improvement in constipation, SIBO and dyspeptics symptoms.
Probiotics Bifidobacterium animalis DN-173010154, Bifidobacterium lactis DN-173 Modulating gut microbiota profile Gut microbiota dysbiosis Shifting the microbial community composition. IBS
Lactobacillus gasseri Improved symptoms and gut transit.
Bile acid sequestrants Obeticholic acid FXR agonist Bile acid alterations Stimulate the synthesis and subsequent release of FGF-19 from ileal epithelial cells and inhibit bile acid synthesis by hepatocytes. IBS-D
Cholestyramine Improve stool form and symptoms of diarrhea.
Bile acid transporter inhibitor Elobixibat IBAT antagonist Bile acid alterations Efficacious treatment for constipation, improving gut transit and symptoms via increasing colonic bile acids. IBS-C
Anti-inflammatory agents Mesalazine Gut immune homeostasis Low grade inflammation Sustained therapy response and benefits for a subgroup of patients with IBS. IBS
Visceral hypersensitivity
Ketotifen Mast cell stabilizer Visceral hypersensitivity Increased the threshold for discomfort in patients with IBS with visceral hypersensitivity, and reduced IBS symptoms. IBS
Ebastine Histamine receptor-1 antagonist Visceral hypersensitivity Reduced visceral hypersensitivity and abdominal pain in patients with IBS. IBS
Acid suppressive therapy Pantoprazole Proton pump inhibitors Gut immune dysfunction Reduced duodenal eosinophilia, mast cells, and intestinal permeability in patients with FD. FD
Epithelial barrier dysfunction
Visceral hypersensitivity
Neuromodulators Amitriptyline TCA Gut-brain dysregulation Affect gastrointestinal motility through anticholinergic and serotonergic mechanisms. TCAs reduce visceral hypersensitivity. Antidepressant therapy might lead to neurogenesis. IBS, FD
Mirtazapine Tetracyclic antidepressants Gut-brain dysregulation Upregulates the levels of orexigenic hormones and downregulated the levels of anorexigenic hormones. FD
Escitalopram SSRI Gut-brain dysregulation Treating depressive symptoms with these molecules modulates the severity of GI symptoms indirectly via a positive effect on depression. IBS
Venlafaxine SNRI
Intestinal Secretagogues Lubiprostone CCl2 agonist Abnormal secretion Increased fecal water content. IBS-C, chronic constipation
Creates an ion gradient that promotes water and sodium secretion into the intestinal lumen.
Linaclotide Guanylate cyclase-C receptor agonist Abnormal secretion Increase water secretion via targeting cGMP leads to the secretion of chloride and bicarbonate into the intestinal lumen. IBS-C
Visceral Analgesics Oliceridine Biased μ-Opioid receptor ligands Visceral hypersensitivity Management of moderate to severe acute pain in adults for whom alternative treatments other than opioids had failed. IBS
Olorinab Cannabinoid type 2 receptor agonist Visceral hypersensitivity Potential analgesic effects in patients with IBS. IBS

DGBIs, disorders of gut-brain interactions; 5-HTR, 5-hydroxytriptamine receptor; GI, gastrointestinal; GCSI, gastroparesis cardinal symptom index; FD, functional dyspepsia; DMV, dorsal motor nucleus of the vagus; IBS-D, diarrhea-predominant irritable bowel syndrome; SIBO, small intestinal bacterial overgrowth; IBS, irritable bowel syndrome; FXR, farnesoid X receptor; FGF-19, fibroblast growth factor 19; IBAT, ileal bile acid transporter; IBS-C, constipation-predominant irritable bowel syndrome; TCA, tricyclic antidepressant; SSRI, serotonin reuptake inhibitor; SNRI, serotonin norepinephrine reuptake inhibitor; CCl2, type 2 chloride channel; cGMP, cyclic guanosine monophosphate.

J Neurogastroenterol Motil 2022;28:357~375
© J Neurogastroenterol Motil