BIOMAT Database Logo BIOMAT Database Logo

Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates. 1996

M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Faculty of Pharmacy, Department of Toxicology, Belgrade, Yugoslavia.

The reaction of human erythrocyte acetylcholinesterase (AChE) with a set of structurally related phosphoramidates was studied in order to investigate the properties of phosphorylated enzyme and the effects of 4 oximes PAM-2, TMB-4, HI-6 and BDB-106 on the reactivation of inhibited AChE. Second-order rate constant of the phosphorylation reaction of the compounds towards the active site of AChE range between 5.0 x 10(2) and 4.9 x 10(6) M-1min-1 and their inhibitory power (I50) was from 7.3 x 10(-5) to 5.7 x 10(-9) M for 20 min incubation at 37 degrees C. The oximes used were weak reactivators of inhibited AChE except for (C4H9O)(NH2)P(O)DCP (DCP, -O-2,5-dichlorphenyl group) and (C6H13O)(NH2)P(O)SCH3 where we have obtained good reactivation. Imidazole oxime BDB-106 proved to be a potent reactivator of tabun-inhibited AChE.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009943 Organophosphorus Compounds Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS. Organophosphorus Compound,Organopyrophosphorus Compound,Organopyrophosphorus Compounds,Compound, Organophosphorus,Compound, Organopyrophosphorus,Compounds, Organophosphorus,Compounds, Organopyrophosphorus
D010091 Oximes Compounds that contain the radical R2C Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D002801 Cholinesterase Reactivators Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates. Insecticides, Organophosphate, Antagonists,Insecticides, Organothiophosphate, Antagonists,Organophosphate Insecticide Antagonists,Organothiophosphate Insecticide Antagonists,Antagonists, Organophosphate Insecticide,Antagonists, Organothiophosphate Insecticide,Insecticide Antagonists, Organophosphate,Insecticide Antagonists, Organothiophosphate,Reactivators, Cholinesterase
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D014289 Trimedoxime Cholinesterase reactivator used as an antidote in alkyl phosphate poisoning. Dipyroxime,TMB-4,Trimedoxime Bromide,Bromide, Trimedoxime

Related Publications

M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Spontaneous and oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates.
January 1988, Archives of toxicology,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Oxime-induced reactivation of acetylcholinesterase inhibited by organophosphinates.
April 1990, Journal of applied toxicology : JAT,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Kinetic analysis of reactivation and aging of human acetylcholinesterase inhibited by different phosphoramidates.
June 2007, Biochemical pharmacology,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Oxime-assisted reactivation of tabun-inhibited acetylcholinesterase analysed by active site mutations.
August 2018, Toxicology,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes.
December 2006, Journal of medical toxicology : official journal of the American College of Medical Toxicology,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Oxime-induced reactivation of carboxylesterase inhibited by organophosphorus compounds.
January 1994, Chemical research in toxicology,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
In vitro oxime reactivation of red blood cell acetylcholinesterase inhibited by methyl-paraoxon.
January 2007, Journal of applied toxicology : JAT,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Acceleration of oxime-induced reactivation of organophosphate-inhibited fetal bovine serum acetylcholinesterase by monoquaternary and bisquaternary ligands.
April 1998, Molecular pharmacology,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
Effect of reversible ligands on oxime-induced reactivation of sarin- and cyclosarin-inhibited human acetylcholinesterase.
February 2015, Toxicology letters,
M Jokanović, and M Maksimović, and V Kilibarda, and D Jovanović, and D Savić
A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds.
March 2013, Chemico-biological interactions,
Copied contents to your clipboard!