title: Effect of a muscarinic M3 receptor agonist on gastric motility.
abstract: Muscarinic M3 receptors exist in the gastrointestinal wall in humans and the muscarinic M3 agonist cevimeline hydrochloride (Evoxac) is a candidate therapeutic agent for the treatment of xerostomia in Sjögren's syndrome. However, M3 receptor agonists are not known to show efficacy for diseases associated with abnormal gastrointestinal motility. Herein the effects are reported of cevimeline on gastric motility in two patients with non-ulcer dyspepsia. The patients both received long-term proton pump inhibitor therapy for 6 months, but their symptoms persisted. Then cevimeline was administered orally for 8 weeks at 30 mg three times daily (90 mg/day) and their dyspepsia symptoms improved. Electrogastrography was performed to examine gastric motility before and after administration of the M3 agonist. The fasting or nocturnal wave rate was significantly increased after administration compared with before administration, but no significant postprandial changes were seen. No adverse effects of cevimeline were observed. This drug might be a candidate therapeutic agent for non-ulcer dyspepsia. Because its postprandial effects on gastrointestinal motility are unclear, a dose-finding clinical study should be performed in the future.
authors.affiliation: The First Department of Internal Medicine, Iwate Medical University, Morioka, Iwate, Japan. toschiba@iwate-med.ac.jp
authors.forename: Toshimi
authors.initials: T
authors.lastname: Chiba
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kudara
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inomata
authors.forename: Seishi
authors.initials: S
authors.lastname: Orii
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D004415:Dyspepsia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use*; D043587:Receptor, Muscarinic M3 / Q000819:agonists* / Q000378:metabolism; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D018721:Muscarinic Agonists; D054328:Proton Pump Inhibitors; D011812:Quinuclidines; D043587:Receptor, Muscarinic M3; D013876:Thiophenes; C059240:cevimeline