Title : A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds.

Pub. Date : 2013 Mar 25

PMID : 22982773






11 Functional Relationships(s)
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1 A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
2 Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus (OP) compounds, which is usually attributed to OP inhibition of acetylcholinesterase (AChE). Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
3 Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus (OP) compounds, which is usually attributed to OP inhibition of acetylcholinesterase (AChE). Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
4 Rate constants for reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and obidoxime, can vary >100-fold between OP-AChE conjugates that are easily reactivated and those that are difficult to reactivate. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
5 Rate constants for reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and obidoxime, can vary >100-fold between OP-AChE conjugates that are easily reactivated and those that are difficult to reactivate. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
6 To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
7 To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
8 Our objective was to identify common mechanism(s) among OP-AChE conjugates of phosphates, phosphonates and phosphoramidates that result in resistance to oxime reactivation. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
9 Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
10 Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens
11 Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. Oximes acetylcholinesterase (Cartwright blood group) Homo sapiens