The protective action of
meptazinol against acute di-isopropyl
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.(ABSTRACT TRUNCATED AT 250 WORDS)