Obidoxime

Obidoxime chloride as insecticide, 2, 516 Obtusilactone H NMR, 4, 578 Occidentalol synthesis, 1, 472 Octaaza[14]annulenes bis w-excessive, 7, 717 Octacoral... 

Obidoxime is an antidote used to treat poisoning with insecticides of the organophosphate type (p. 102). Phosphorylation of acetylcholinesterase causes an irreversible inhibition of ace-Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Therapeutic measures include 1. administration of atropine in high dosage to shield muscarinic acetylcholine receptors and 2. reactivation of acetylcholinesterase by obidoxime, which successively binds to the enzyme, captures the phosphate residue by a nucleophilic attack, and then dissociates from the active center to release the enzyme from inhibition. 

Another possibility to treat a poisoning with esterase inhibitors of the organophosphorous type are the so called esterase reactivators compounds with an oxime structure like obidoxime and prali-doxime. The oxime moiety has a very high affinity for the phosphorous atom and can thereby under certain circumstances hydrolyze the otherwise stable organophosphorous-enzyme complex. 

Barckow, D., Neuhaus, G., and Erdmann, W.D. Zur Behandlung der schweren Parathion-(E 6050O)-Verglftung mlt dem Cholin-esterase-Reaktivator Obidoxim (Toxogonin )). Arch. Toxikol. 24 133-146, 1969. (English Summary)... 

Simon, G.A., Tlrosh, M.S., and Edery, H. Administration of obidoxime tablets to man. Plasma levels and side reactions. 

USP2996510, 59MI20900) all exhibit cholinesterase reactivation. Obidoxime chloride (52), based on the 4-aldoxime, has a similar function. 

The ketoxime derivative fluvoxamine (12) is a newer antidepressant thought to potentiate the action of 5-hydroxytryptamine76. Oxacillin (13), cefuroxime (14) as well as the monobactam aztreonam (15) represent potent antibacterial agents of the beta-lactam type77. The aldoxime pralidoxime (16) and a number of bi.v-quarternary oximes, such as obidoxime (17), can be used as reactivators of the phosphorylated esteratic site of acetylcholinesterase that occurs in the presence of organophosphate inhibitors78,79. 

FIGURE 5.13 Autocatalytic reaction of obidoxime chloride with k = 3.27 x lO mLfmg-wk)-1 (a) concentration vs. time and (b) rate vs. time. [Graph reconstructed from data by Rubnov et al., J. Pharm. Pharmcol., 51, 9 (1999).]... 

Cholinesterase inhibition, the mechanism whereby a number of insecticides and nerve gases function, may be reversed by acid salts of pyridine-2-carbaldehyde oxime (51). The chloride (61JPS109, 64USP3155674), iodide (57USP2816113) and methanesulfonate (58USP2996510. 59MI20900) all exhibit cholinesterase reactivation. Obidoxime chloride (52), based on the 4-aldoxime, has a similar function. 

Figure 9.18. Reactivation of DFP-reacted cholinesterase with hydroxylamine, and stractures of the two related dmgs pralidoxime and obidoxime, which are clinically used in organophosphate poisoning.

Acinitrazole, barban, carbidopa, dinitro-orthocresol (100°), dinobuton, dinoseb, do-decyl gallate, hexoprenaline (— brown), iso-prenaline (— yellow), nifedipine, nifuratel, nifursol, obidoxime, protokylol (— yellow)... 

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