reactivation effect of pralidoxime in human blood on parathion and paraoxon-induced cholinesterase inhibition

In this investigation the reactivation of cholinesterases by pralidoxime in parathion and paraoxon intoxication in plasma and erythrocytes were studied. For this purpose, human plasma and erythrocytes were incubated with various concentrations of parathion [0.1-10 micro M] and paraoxon [0.03-0.3 micro M] at 37 °C for 10 min. Then, pralidoxime [10-300 micro M] was added to the samples and incubated for 10 min before cholinesterases assay. The results showed that effects of parathion and paraoxon were dose dependent. These agents inhibited more than 85% of butyrylcholinesterase [BChE] and acetylcholinesterase [AChE] activity and the inhibitory effect of paraoxon was 10 times more than parathion. BChE activity was significantly higher than the control at 100 micro M of pralidoxime and it reduced inhibitory effects of parathion to less than 50% and of paraoxon to 42% of control. When pralidoxime [10 micro M] was added to erythrocytes, the inhibitory effects of two organophosphates were reduced to less than 15%. At higher concentrations of pralidoxime [>100 micro M], both BChE and AChE activities were inhibited

Pralidoxime as an insignificant reactivator in severe anticholinesterase (organophosphate insecticide) poisoning.

In acute severe anticholinesterase poisoning by organophosphate compounds, pralidoxime (P-2-AM, pyridine-2-aldoxime methiodide) used in the recommended doses, intravenously, has not been shown to reactivate the inhibited cholinesterase, as evidenced both clinically and biochemically. In vitro studies using pralidoxime iodide up to ten times the recommended concentrations, produced insignificant reactivation of cholinesterases inhibited by the organophosphate insecticide Bidrin (di-methyl-3-hydroxyl-N, N-dimethyl-crotonamide phosphate). This was even so despite prolonged exposure of the inhibited cholinesterases to the oxime. The value of pralidoxime as a reactivator of phosphorylated cholinesterases is therefore in doubt, and should not be used in preference to large doses of atropine and other supportive treatment in poisoning by organophosphate insecticides.

Reactivation studies on organophosphate inhibited human cholinesterases by pralidoxime (P-2-AM).

There is biochemical and clinical evidence that P-2-AM (Pyridine-2-Aldoxime Methiodide, Pralidoxime) does not reactive human acetylcholinesterase inhibited by either Malathion or Malaoxon. In vitro studies using Pralidoxime iodide up to ten times the recommended concentrations, produced insignificant reactivation of cholinesterases inhibited by Malathion or Malaoxon. This was observed inspite of prolonged exposure of the inhibited cholinesterases to the oxime. The value of Pralidoxime as a reactivator of phosphorylated cholinesterases is therefore in doubt, and should not be used in preference to large doses of atropine and other supportive treatment in poisoning by organophosphate pesticides.