In vivo inhibition of rabbit whole blood cholinesterase following intravenous infusion of a diethyl organophosphate inhibitor and reactivation with 2-PAM
| Autor: | Thomas E. Shellenberger, R.M. Bridgman, Gordon W. Newell |
|---|---|
| Rok vydání: | 1965 |
| Předmět: |
chemistry.chemical_classification
Pralidoxime Compounds biology Organophosphate Active site General Medicine Pharmacology Phosphate General Biochemistry Genetics and Molecular Biology Enzyme assay Enzymes Phosphates chemistry.chemical_compound Enzyme Biochemistry chemistry In vivo biology.protein Animals Cholinesterases Cholinesterase Inhibitors Rabbits General Pharmacology Toxicology and Pharmaceutics Cholinesterase Whole blood |
| Zdroj: | Life sciences. 4(20) |
| ISSN: | 0024-3205 |
| Popis: | It is now generally accepted that the reaction of a dialkyl organophosphate with cholinesterase involves phosphorylation with the active site of the enzyme. Subsequent reactions of the phosphorylated enzyme include spontaneous reactivation and conversion, apparently first order, to a non-reversible or “aged” enzyme. The extent of these reactions is dependent on the alkyl substituents of the inhibitor and the enzyme source. Vandekar and Heath (1, 2) reported marked differences in the recovery rate of brain and erythrocyte cholinesterase activity following inhibition with “persistent” and “non-persistent” dimethyl phosphate inhibitors; enzyme recovery was more rapid after inhibition by the “non-persistent” inhibitors. However, spontaneous recovery of the enzyme, inhibited by “non-persistent” inhibitors, was markedly reduced following continuous intravenous infusion of the materials for several hours. These workers also reported that the spontaneous recovery of enzyme activity was high following short periods of compound infusion, which has been confirmed by Shellenberger et al. (2), using three dimethyl phosphate inhibitors. When these compounds were infused intravenously into rabbits for 2 hours or less, there was rapid but incomplete recovery of inhibited whole blood cholinesterase during the immediate post-infusion period. The spontaneous reactivation of diethyl-phosphoryl cholinesterase is generally of low magnitude, even though it may occur over several days (3). The reversal of diisopropyl-phosphoryl enzyme is negligible. However, the reversal depends on both the inhibitor and the enzyme source. Species differences and differences between true and pseudo-cholinesterase reactivation have been demonstrated. In the current study, rabbit whole blood cholinesterase was rapidly and almost completely inhibited during intravenous infusion of 2, 2-dichlorovinyl diethyl phosphate. There was little, if any, spontaneous reversal of inhibited enzyme during a subsequent 3-hour postinfusion period. Intravenous injection of 2-PAM immediately and up to 2 hours after infusion produced an immediate partial recovery of enzyme activity. The extent of recovery was directly related to the dosage level of injected reactivator. |
| Databáze: | OpenAIRE |
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