Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating and changes in the consistency of bowel movements. These symptoms may occur over a long time, sometimes for years. IBS can negatively affect quality of life and may result in missed school or work or reduced productivity at work. Disorders such as anxiety, major depression, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are common among people with IBS.
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.
Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. It has been sold under the trade names Prepulsid (Janssen-Ortho) and Propulsid (in the United States). It was discovered by Janssen Pharmaceuticals in 1980. In many countries, it has been either withdrawn from the market or had its indications limited due to incidence of serious cardiac side-effects. Propulsid was linked to children's deaths.
Functional gastrointestinal disorders (FGID), also known as disorders of gut–brain interaction, include a number of separate idiopathic disorders which affect different parts of the gastrointestinal tract and involve visceral hypersensitivity and motility disturbances.
Functional constipation, also known as chronic idiopathic constipation (CIC), is defined by less than three bowel movements per week, hard stools, severe straining, the sensation of anorectal blockage, the feeling of incomplete evacuation, and the need for manual maneuvers during feces, without organic abnormalities. Many illnesses, including endocrine, metabolic, neurological, mental, and gastrointestinal obstructions, can cause constipation as a secondary symptom. When there is no such cause, functional constipation is diagnosed.
Alosetron, sold under the brand name Lotronex among others, is a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in females only.
Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon, which is rich with bacteria, the small bowel usually has fewer than 100,000 organisms per millilitre. Patients with bacterial overgrowth typically develop symptoms which may include nausea, bloating, vomiting, diarrhea, malnutrition, weight loss, and malabsorption by various mechanisms.
Renzapride is a prokinetic agent and antiemetic which acts as a full 5-HT4 agonist and partial 5-HT3 antagonist. It also functions as a 5-HT2B antagonist and has some affinity for the 5-HT2A and 5-HT2C receptors.
Rifaximin, sold under the brand name Xifaxan among others, is a non-absorbable, broad-spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It was developed by Salix Pharmaceuticals.
Lubiprostone, sold under the brand name Amitiza among others, is a medication used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation. The drug is owned by Mallinckrodt and is marketed by Takeda Pharmaceutical Company.
Donnatal is a combination medication that provides natural belladonna alkaloids in a specific fixed ratio combined with phenobarbital to provide peripheral anticholinergic/antispasmodic action and mild sedation. Donnatal is manufactured for Concordia Pharmaceuticals by IriSys, LLC. It is available as tablets and 5 mL elixir. Active ingredients are listed as: phenobarbital (16.2 mg), hyoscyamine sulfate (0.1037 mg), atropine sulfate (0.0194 mg), and scopolamine hydrobromide (0.0065 mg). The latter two ingredients are found in plants of the family Solanaceae, such as belladonna.
Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates emptying throughout the whole of the gastrointestinal tract in humans, and is used for the treatment of gastritis, gastroesophageal reflux disease, functional dyspepsia and irritable bowel syndrome. It is recommended to be taken on an empty stomach (i.e. at least one hour before food or two hours after food).
Solabegron is a drug which acts as a selective agonist for the β3 adrenergic receptor. It is being developed for the treatment of overactive bladder and irritable bowel syndrome. It has been shown to produce visceral analgesia by releasing somatostatin from adipocytes.
Prucalopride, sold under brand names Resolor and Motegrity among others, is a medication acting as a selective, high affinity 5-HT4 receptor agonist which targets the impaired motility associated with chronic constipation, thus normalizing bowel movements. Prucalopride was approved for medical use in the European Union in 2009, in Canada in 2011, in Israel in 2014, and in the United States in December 2018. The drug has also been tested for the treatment of chronic intestinal pseudo-obstruction.
Levosulpiride, sold under the brand names Dislep and Sulpepta among others, is a dopamine antagonist medication which is used in the treatment of psychotic disorders like schizophrenia, major depressive disorder, nausea and vomiting, and gastroparesis. It is taken by mouth.
A prokinetic agent is a type of drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhythm. They are used to treat certain gastrointestinal symptoms, including abdominal discomfort, bloating, constipation, heart burn, nausea, and vomiting; and certain gastrointestinal disorders, including irritable bowel syndrome, gastritis, gastroparesis, and functional dyspepsia.
Velusetrag (INN, USAN; previously known as TD-5108) is an experimental drug candidate for the treatment of gastric neuromuscular disorders including gastroparesis, and lower gastrointestinal motility disorders including chronic idiopathic constipation and irritable bowel syndrome. It is a potent, selective, high efficacy 5-HT4 receptor serotonin agonist being developed by Theravance Biopharma and Alfa Wassermann. Velusetrag demonstrates less selectivity for other serotonin receptors, such as 5-HT2 and 5-HT3, to earlier generation 5-HT agonists like cisapride and tegaserod.
Eluxadoline, sold under the brand names Viberzi and Truberzi, is a medication taken by mouth for the treatment of diarrhea and abdominal pain in individuals with diarrhea-predominant irritable bowel syndrome (IBS-D). It was approved for use in the United States in 2015. The drug originated from Janssen Pharmaceutica and was developed by Actavis.
Plecanatide, sold under the brand name Trulance, is a medication for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. It is available in India under the brand name Plectide. Plecanatide is an agonist of guanylate cyclase-C. Plecanatide increases intestinal transit and fluid through a buildup of cGMP.
Olorinab (APD371) is a drug being developed by Arena Pharmaceuticals for the treatment of gastrointestinal pain associated with Crohn's disease and irritable bowel syndrome. It acts as a potent and selective cannabinoid CB2 receptor agonist and is claimed to be orally active and peripherally selective. Initial Phase IIa exploratory clinical trials have been successful in patients with quiescent Crohn's disease. Arena initiated the Phase IIb Captivate trial in late July 2019 in patients with irritable bowel syndrome related pain, in constipation and diarrhea predominant sub-types. The Phase IIb trial is expected to enroll 240 participants between the ages of 18 and 70.Three doses of 10 mg, 25 mg, and 50 mg are being tested against Placebo in a 3:4 prescription ratio with a Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) masking layout.
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