1 Multiple low doses of the direct acting organopho sphates, ecothiopate, paraoxon and mipafox produced persistent and additive inhibition of diaphragm acetylcholinesterase. Paraoxon and mipafox had similar effects on brain acetylcholinesterase. There was greater recovery from inhibition between doses for paraoxon and ecothiopate than for mipafox.
2 Ecothiopate did not inhibit brain acetylcholinesterase but there was a small increase in activity.
3 Mipafox also had a cumulative inhibitory effect on brain neuropathy target esterase.
4 These results have particular implication for the use of multiple low doses of organophosphates occupation- ally by man.
Kelly SS, deBlaquiere G., Williams FM, Blain PGEffects of multiple doses of organophosphates on evoked potentials in mouse diaphragm Submitted to Human and Exper Toxicol (1997).
2.
Ellman GL, Courtney K., Andres V. Jr, Featherstone R.A new and rapid colorimetric determination of acetylcholinesterase activityBiochem Pharmacol1961; 7: 89-95.
3.
Mutch E., Kelly SS, Blain PG, Williams FMComparative studies of two organophosphorus compounds in the mouseToxicology Letters1996; 81: 45 - 53.
4.
Lintern MC, Smith ME, Ferry CBThe effect of repeated treatment with physostigmine on the activity of acetylcholinesterase molecular forms in mouse skeletal muscleBrit J Pharmacol1995; 116: 814.
5.
Gallo MA, Lawryk NJOrganophosphorus pesticides In Handbook of Pesticide Toxicology vol 2 ed Hayes WJ and Laws ER, London: Academic press 2 pp. 917-1123, 1991.
6.
Davison ANReturn of cholinesterase activity in the rat after inhibition by organophosphorus compoundsJ Biochem1955; 60: 339-46.
7.
Eigenberg DA , Pozdernik TL, Doull J.Hemoperfusion and pharmacokinetic studies with parathion and paraoxon in the rat and dogDrug Metab Dispos1983; 11: 366-70.
8.
Younkin SG, Rosenstein C., Collins PL, Rosenberry TLCellular localisation of the molecular forms of acetylcholinesterase in rat diaphragmJ Biol Chem1982; 257: 13630-7.
9.
Ogane N., Giacobini E., Messamore E.Preferential inhibition of acetylcholinesterase molecular forms in rat brainNeurochem Res1992; 17: 489-95.
10.
Milatovic D. , Dettbarn WDModification of acetylcholinesterase during adaptation to chronic, subacute paraoxon application in ratToxicology and Applied Pharmacology1996; 136: 20-8.
11.
Kelly SS et al. Electrophysiological changes in the neuromuscular system and biochemical effects following single doses of organophosphates in the mouseArch Toxicol1994; 68: 459-66.
