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.