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Main Title Correlation of the Anticholinesterase Activity of a Series of Organophosphates with Their Ability to Compete with Agonist Binding to Muscarinic Receptors.
Author Ward, T. R. ; Ferris, D. J. ; Tilson, H. A. ; Mundy, W. R. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC.
Publisher c1993
Year Published 1993
Report Number EPA/600/J-94/067;
Stock Number PB94-144615
Additional Subjects Organophosphorus compounds ; Cholinesterase inhibitors ; Muscarinic receptors ; Competitive binding ; Acetylcholinesterase ; Quinuclidinyl benzilate ; Echothiophate iodide ; Cerebral cortex ; Hippocampus ; Malathion ; Disulfoton ; Reprints ; Cis-methyldioxolane ; Malaoxan
Library Call Number Additional Info Location Last
NTIS  PB94-144615 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 10p
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. The interaction of eight organophosphates 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. Of the compounds tested only echothiophate competed for (3H)QNB binding and only at concentrations greater than 100 microM. The anticholinesterase compounds were also tested for their ability to compete with a muscarinic receptor agonist, (3H)CD, which binds with high affinity to 10 and 3% of the muscarinic receptors in the frontal cortex and hippocampus, respectively. The anticholinesterase compounds inhibited high-affinity (3H)CD binding up to 80% and the effects were similar in both tissues. A strong correlation was found between the ability of a compound to inhibit AChE activity and the ability to compete with (3H)CD binding. These data suggest that the biological effects of cholinesterase-inhibiting compounds may be due to more than their ability to inhibit AChE.