ドパミンD₂受容体拮抗剤の抗コリンエステラーゼ活性: その臨床的意義

抄録

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, ciaspride did not always induce the interdigestive migrating contrac-tions (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-cholinestrase activity was found in domperidone, the activity being about 1/1, 000 of that of neostigmine. In dog experiment, similar enhance-ment of motor stimulating activity of cisapride was observed when neostigmine was given at 1.0 μg/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.