[The relevance of anticholinesterase properties to toxicity and neuromuscular effects of sulpiride (author's transl)].
N-[(1-Ethyl-pyrrolidin-2-yl)-methyl]-2-methoxy-5-sulf-amoyl-benzamide (sulpiride, Dogmatil) inhibits acetylcholinesterase of rat brain in a mixed-type manner (Ki 0.3 mM; Ki 1.8 mM) as well as serum cholinesterase of the rat competitively (Ki 0.37 mM). Using acetylthiocholine in concentrations below 0.1 mM and purified enzyme from Electrophorus, reaction becomes first-order kinetics. At 35 micronM sulpiride doubles half-life and is without effects below 3.5 micronM. Hydrolysis of acetylthiocholine in homogenates of stomach muscle from rats is not affected by sulpiride up to 20 micronM. Pretreatment of mice with 5 mg atropine/kg i.p. decreases i.p. LD50 of sulpiride to 67% of controls. The conclusion is drawn that neither toxicity nor hypermotility of stomach seen after sulpiride by other authors is due to the cholinesterase inhibiting properties of sulpiride.
D000122:Acetylthiocholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000097:blood; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D013469:Sulpiride / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D000122:Acetylthiocholine; D001285:Atropine; D013469:Sulpiride; D002802:Cholinesterases
Die Bedeutung der cholinesterasehemmendren Eigenschaften für Toxizität und neuromuskuläre Wirkungen von Sulpirid