Effects of KW-5092, a novel gastroprokinetic agent, on intestinal water and electrolyte transport in rats.
KW-5092 ([1-[2-[[[5-(piperidinomethyl)- 2-furanyl]methyl]amino]ethyl]-2-imidazolidinylidene]propanedini trile fumarate) enhances acetylcholine release from enteric neurons and inhibits acetylcholinesterase (AChE), resulting in the enhancement of a wide range of gastrointestinal motilities. The present study examined the effects of KW-5092 on intestinal water and electrolyte transport in rats. In the jejunum, oral or intrajejunal administration of the laxative bisacodyl (30 mg/kg) significantly inhibited absorption of water, Na+ and Cl-, and significantly enhanced K+ secretion. In contrast, neither KW-5092 (1-30 mg/kg) nor the AChE inhibitor neostigmine (0.3-10 mg/kg), orally or intrajejunally administered, affected water or electrolyte transport in the jejunum. Similar results were obtained in the colon when the drugs were applied orally or intracolonically. Moreover, neither KW-5092 (1-30 mg/kg, p.o.) nor neostigmine (0.3-10 mg/kg, p.o.) induced diarrhea, while bisacodyl (30 mg/kg, p.o.) induced diarrhea in all the rats examined. These results demonstrate that KW-5092 or neostigmine at the gastroprokinetic doses does not affect intestinal water or electrolyte transport in rats, suggesting that cholinergic activation enhances gastrointestinal motility rather than intestinal secretion of water and electrolytes.
Kishibayashi
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N
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa, Shizuoka, Japan.
Karasawa
A
A
D000818:Animals; D001726:Bisacodyl / Q000494:pharmacology; D002400:Cathartics / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007408:Intestinal Absorption; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000378:metabolism*
D002400:Cathartics; D002800:Cholinesterase Inhibitors; D004573:Electrolytes; D005765:Gastrointestinal Agents; D007093:Imidazoles; D009570:Nitriles; D014867:Water; D001726:Bisacodyl; C081341:KW 5092; D009388:Neostigmine