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CORRELATION OF THE ANTICHOLINESTERASE ACTIVITY OF A SERIES OF ORGANOPHOSPHATES WITH THEIR ABILITY TO COMPETE WITH AGONIST BINDING TO MUSCARINIC RECEPTORS
Citation:
Ward, T., D. Ferris, H. Tilson, AND W. Mundy. CORRELATION OF THE ANTICHOLINESTERASE ACTIVITY OF A SERIES OF ORGANOPHOSPHATES WITH THEIR ABILITY TO COMPETE WITH AGONIST BINDING TO MUSCARINIC RECEPTORS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/067 (NTIS PB94144615), 1993.
Description:
Some compounds that inhibit acetylcholinesterase (ACHE) activity compete directly with quinuclidinyl benzilate (QNB) binding, a muscarinic antagonist which binds to all subtypes equally, and with cis-methyldioxolane (CD), an agonist that binds with high affinity to the M2 subtype of muscarinic receptors. he relationship between inhibition of ACHE activity and the capability to affect muscarinic receptors directly has not been systematically explored. he interaction of eight organophosphates (OPs) with muscarinic receptors was compared to their ability to inhibit ACHE activity in vitro in tissue homogenates from rat hippocampus and frontal cortex, two cholinergically enriched areas of the brain. f the compounds tested only echothiophate competed for [3H]QNB binding and only at concentrations greater than 100um. he anticholi-nesterase compounds were also tested for their ability to compete with another muscarinic receptor agonist, [3H]CD, which binds with high affinity (approximate KD+3.5 nM) to 10% and of the muscarinic receptors in the frontal cortex and hippocampus, respectively. he anticholinesterase compounds inhibited high affinity HICD binding up to 80% and the effects were similar in both issues. Echothiophate and DFP were potent inhibitors of [3H]CD binding, as were the active "axon" forms of parathion, malathion and disulfoton. he parent "thio" forms of these insecticides, however, were much less effective in competing for [3H]CD binding. imilar pattern of potency was observed for the inhibition of brain kChE activity. trong correlation was found between the ability of a compound AChE activity and to compete with [3H]CD binding.