Comparative studies of two organophosphorus compounds in the mouse.
A rodent model, the albino mouse, was used to investigate the in vitro and in vivo capacity of 2 organophosphate (OP) compounds, mipafox and ecothiopate, to inhibit enzymes considered to be involved in the mechanisms of OP toxicity. Mipafox and ecothiopate were chosen as model compounds because the former can produce a delayed neuropathy whereas the latter does not. Mipafox (110 mumol/kg, s.c.) inhibited brain acetylcholinesterase (AChE), neuropathy target esterase (NTE) and phenylvalerate hydrolases by 58, 64 and 65%, while diaphragm AChE and phenylvalerate hydrolases were inhibited by 66 and 80%, respectively. In contrast, ecothiopate (0.5 mumol/kg) had no effect on brain NTE or on brain or diaphragm phenylvalerate hydrolases. At the same time, diaphragm AChE was inhibited by 60% while brain AChE activity had increased by 15% of control. Mipafox was a potent inhibitor of AChE and NTE in vitro. Although ecothiopate was a highly potent anti-ChE in vitro, it had no inhibitory effect on NTE.
Mutch
E
E
Department of Environmental and Occupational Medicine, Medical School, Newcastle University, UK.
Kelly
S S
SS
Blain
P G
PG
Williams
F M
FM
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D003964:Diaphragm / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004456:Echothiophate Iodide / Q000008:administration & dosage / Q000633:toxicity*; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051379:Mice; D012044:Regression Analysis
D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; C005238:mipafox; D004456:Echothiophate Iodide; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase