Anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319.
The anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319 (QB) was studied in vitro. QB proved to be a noncompetitive inhibitor of both acetylcholinesterase (or true cholinesterase) and butyrylcholinesterase (or pseudocholinesterase) having a KI = 0.5 X 10(-6) M for acetylcholinesterase and 1.5 X 10(-6) M for butyrylcholinesterase. Further, QB inhibited esterase activity of murine plasma in a noncompetitive manner (KI = 4.2 X 10(-6) M). The inhibition was instantaneous in onset and did not diminish with prolonged incubation of the drug and enzyme. All mice treated intravenously with 2 mg QB/kg died within 5 min. Prior to death, mice developed severe parasympathomimetic effects and convulsions. Although the parasympathomimetic effects were diminished by atropine sulfate pretreatment, death could only be prevented by barbiturate anesthesia.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases; D004950:Esterases / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D051379:Mice; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011806:Quinolinium Compounds / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D011806:Quinolinium Compounds; C018435:quinolinium dibromide; D004950:Esterases; D002802:Cholinesterases