Gastrointestinal motility modulating drugs include all compounds which have pharmacological

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1 Pharmacotherapeutics Gastrointestinal Motility Modulating Drugs Oh Young Lee, MD Department of Internal Medicine, Hanyang University College of Medicine E - mail : leeoy@hanyang.ac.kr J Korean Med Assoc 2009; 52(9): Abstract Gastrointestinal motility modulating drugs include all compounds which have pharmacological activity of modulating (stimulating or inhibiting) gastrointestinal motility. They are mainly used for the treatment of functional gastrointestinal diseases. Gastrointestinal motility modulating drugs include 5HT receptor agonists, antagonists, and antidopaminergic agents. Many new gastrointestinal motility modulating drugs are currently under investigation. The aims of this article are to review the mechanism of action, efficacy and side effects of the gastrointestinal motility modulating drugs. Keywords: Motility modulating drugs; Pharmacotherapy; Prokinetics; Functional gastrointestinal diseases 920

2 Gastrointestinal Motility Modulating Drugs Table 1. Pharmacodynamic properties, gastrointestinal motor effects and side effects of gastrointestinal modulating drugs Classification and Target receptors Gastrointestinal motor effects Side effects name of drugs and actions Esophagus Stomach Colon Dopamine D 2 R AT Metoclopramide Dopamine D 2 R AT, contraction GET extrapyramidal Sx 5HT 4 AG, 5HT 3 AT hyperprolactemia associated Sx Domperidone Dopamine D 2 R AT LES pr GET hyperprolactemia associated Sx Itopride Dopamine D 2 R AT,? GET? rash, diarrhea, gliddiness, inhibition of galactorrhea acethylcholinesterase Levosulpiride Dopamine D 2 R AT,? GET hyperprolactemia associated Sx 5HT 4 AG, weak 5HT 3 AT 5HT 4 R AG Cisapride 5HT 4 R AG, contraction, GET CTT QT prolongation weak 5HT 3 R AT LES pr Mosapride 5HT 4 R AG, metabolite:? GET? weak 5HT 3 R AT Tegaserod 5HT 4 R AG? GET, GA CTT abdominal pain, headache, heart attack Prucalopride 5HT 4 R AG?? CTT abdominal pain Renzapride 5HT 4 R AG, 5HT 1,? GET CTT abdominal pain, headache 5HT 3 R AT Motilin R AG Erythromycin Motilin R AG LES pr GET, GA arrythmia, reversible deafness, abdominal pain, diarrhea 5HT 1A R AG Buspirone 5HT 1 A R AG GET, GA vertigo, headache, agitation 5HT 1B/D R AG Sumatriptan 5HT 1B/D R AG GET, GA palpitation, syncope, anemia, myalgia 5HT 3 R AT Alosetron 5HT 3 R AT CTT ischemic colitis Cilansetron 5HT 3 R AT CTT ischemic colitis Ondansetron 5HT 3 R AT CTT dizziness, headache SSRI Citalopram contractility fatigue, drowsiness, dry mouth, headache Paroxetine GA nausea, somnolence, dizziness, dry mouth GABA B receptor AG Baclofen GABA B R AG TLESR headache, dizziness, insomnia, nausea, constipation Phosphodiesterase-5 inhibitors Sildenafil Phosphodiesterase -5 GA headache, flushing, dyspepsia, inhibitors nasal congestion, photophobia Nitrate Nitroglycerin GA headache, painful urination, dizziness R: receptor, Sx: symptom, Pr: pressure, AG: agonist, AT: antagonist SSRI: selective serotonin reuptake inhibitor GET (gastric emptying time) : accelerate, :delay CTT (colon transit time) : accelerate, : delay LES: low esophageal sphincter TLESR : reduces transient low esophageal sphincter relaxation GA (gastric accomodation) : enhance, : decrease 921

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4 Gastrointestinal Motility Modulating Drugs 923

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6 Gastrointestinal Motility Modulating Drugs 925

7 Lee OY 11. Karamanolis G, Tack J. Promotility medication-now and in the future. Dig Dis 2006; 24: Tonini M, Cipollina L, Poluzzi E, Crema F, Corazza GR, De Ponti F. Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther 2004; 19: Tack J. Prokinetics and fundic relaxants in upper functional GI disorders. Curr Opin Pharmacol : Kindt S, Tack J. Mechanisms of serotonergic agents for treatment of gastrointestinal motility and functional bowel 926

8 Gastrointestinal Motility Modulating Drugs disorders. Neuogastroenterol Motility 2007; 19: Costedio MM, Hyman N, Mawe GM. Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum 2007; 50: Peer Reviewers Commentary 927

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