title: Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.
abstract: Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.
authors.affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Teita
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Aida
authors.affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Suemasu
authors.affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tahara
authors.affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.|LTT Bio-Pharma Co., Ltd, Shiodome Building 3F, 1-2-20 Kaigan, Minato-ku, Tokyo 105-0022, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000481:Allantoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000818:Animals; D004415:Dyspepsia / Q000188:drug therapy* / Q000503:physiopathology*; D005746:Gastric Emptying / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D000481:Allantoin; D000536:Aluminum Hydroxide; C017231:aldioxa