Protection of acetylcholinesterase by meptazinol in mice exposed to di-isopropyl fluorophosphate. Comparison with physostigmine

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Abstract
The protective action of meptazinol against acute diisopropyl fluorophosphate (DFP) intoxication has been evaluated in mice by measuring the effects on the DFP LD50 of the pretreatment of the animals with increasing doses of the drug. Meptazinol at the doses 15, 30 and 45 mg kg−1 injected 15 min before DFP caused a dose-dependent increase in the DFP LD50, resulting in protection ratios equal to 2.1, 4.8 and 9.7, respectively, in the absence of atropine and 2.5, 4.7 and 8, respectively, in the presence of atropine sulphate (17.4 mg kg−1) therapy. Under the same experimental conditions, the protective ratio of 0.1 mg kg−1 physostigmine sulphate was 2.2 and 7.3 in the absence and presence of atropine therapy, respectively. In separate experiments, the time course of acetylcholinesterase (AChE) activity recovery was evaluated in the brain and diaphragm of mice pretreated with meptazinol (30 mg kg−1) or physostigmine (0.1 mg kg−1) 15 min before poisoning with DFP (8 mg kg−1). Ten minutes after poisoning, residual AChE activity in the brain averaged 4, 47 and 15% of that in controls in animals pretreated with atropine alone, atropine plus meptazinol or atropine plus physostigmine, respectively. Twenty four hours after poisoning, brain AChE activity averaged 31 and 47% of that in controls in mice protected by meptazinol and physostigmine, respectively. The data from the diaphragm closely paralleled those from the brain. It is concluded that high doses of meptazinol exert antidotal action against acute DFP poisoning in the mouse comparable in efficacy with that of physostigmine combined with atropine. This action is most probably due to the ability of meptazinol to protect AChE from irreversible inactivation by DFP.

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