Effects of KW-5092 on antroduodenal coordination and gastric emptying in guinea-pigs.
KW-5092 (2-[1-[2-[[5-(piperidinomethyl)-2-furanyl] methylamino]ethyl]imidazonylidin-2-ylidenene]malononitrile fumarate) is a novel gastroprokinetic agent with both acetylcholine release facilitatory and acetylcholinesterase inhibitory activity. We have investigated the effects of KW-5092 on antroduodenal coordination and gastric emptying in guinea-pigs. In the guinea-pig isolated gastroduodenal preparation, KW-5092 at 3 x 10(-7) to 3 x 10(-6) M significantly increased antroduodenal coordination. The effect of KW-5092 was almost completely inhibited by atropine or tetrodotoxin. Cisapride, a gastroprokinetic agent with acetylcholine release facilitatory activity, also increased coordination whereas neither acetylcholine nor the acetylcholinesterase inhibitor neostigmine affected it. In-vivo, KW-5092 and cisapride enhanced gastric emptying whereas neostigmine delayed it. These results suggest that acetylcholine release facilitation, but not acetylcholinesterase inhibition, is involved in the enhancement by KW-5092 of antroduodenal coordination and gastric emptying.
Kishibayashi
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Department of Pharmacology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd, Shizuoka, Japan.
Karasawa
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A
D000284:Administration, Oral; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D020117:Cisapride / Q000494:pharmacology; D004347:Drug Interactions; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D005765:Gastrointestinal Agents; D007093:Imidazoles; D009570:Nitriles; C081341:KW 5092; D009388:Neostigmine; D020117:Cisapride