[Anti-cholinesterase activity of dopamine D2 receptor antagonist: its clinical significance].
Anti-cholinesterase activity of dopamine D2 receptor antagonist, domperidone was studied by means of chronically implanted force transducers in the gastrointestinal (GI) tract in five conscious dogs. Cisapride was used as a drug to stimulate endogenous release of acetylcholine. In the digestive state, cisapride (0.25 mg/kg) stimulated 18.6 +/- 5.6% increase in the motor index of the gastric antrum alone, however, combined administration with domperidone (1.0 mg/kg-hr) significantly enhanced the motor index in the gastric antrum and duodenum. In the gastric antrum, the increase was 68.1 +/- 7.2%. During the interdigestive state, cisapride did not always induce the interdigestive migrating contractions (IMC)-like contractions in the GI tract, but the background infusion of domperidone significantly increased the incidence of the occurrence of IMC-like contractions by cisapride. In in vitro study, weak but significant anti-cholinesterase activity was found in domperidone, the activity being about 1/1,000 of that of neostigmine. In dog experiment, similar enhancement of motor stimulating activity of cisapride was observed when neostigmine was given at 1.0 micrograms/kg-hr. In conclusion, domperidone has anti-cholinesterase activity and acts to enhance motor stimulating activity of cisapride through inhibition of cholinesterase activity in the upper digestive tract.
Mizumoto
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A
GI Laboratories, College of Medical Technology, Gunma University, Maebashi.
Itoh
Z
Z
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors; D020117:Cisapride; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D010880:Piperidines; D009388:Neostigmine; D004294:Domperidone; D001285:Atropine; D000109:Acetylcholine; D020117:Cisapride