ISSN:
1432-0738
Keywords:
1,2,3,4-Tetrahydro-9-aminoacridine
;
Diisopropylfluorophosphate
;
Physostigmine
;
Pyridostigmine
;
Acetylcholinesterase protection
;
Organophosphorus intoxication
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The protective action of 1,2,3,4-tetrahydro-9-aminoacridine (THA) against acute diisopropylfluorophosphate (DFP) intoxication was evaluated in mice by measuring the effects of the pretreatment of the animals with various doses of the drug on the DFP LD50. In the same experiments, the action of physostigmine and pyridostigmine were compared. THA at the doses 2.5, 5 and 7.5 mg/kg injected subcutaneously 15 min before DFP caused a dose-dependent increase in the DFP LD50, resulting in protection ratios equal to 3, 3.1 and 4.4, respectively, in the absence of atropine and 4.5, 8.6 and 14.5, respectively, in the presence of atropine sulfate (17.4 mg/kg) therapy. Under the same experimental conditions, the protective ratios of 0.1 mg/kg physostigmine and pyridostigmine were 2.2 and 1.3, respectively, without atropine and 11.0 and 12.2, respectively, with atropine. The effectiveness of THA antidotal effect was inversely correlated to the time between pretreatment and DFP administration, being maximal when THA was injected 15 min before poisoning. In separate experiments, the time-course of acetylcholinesterase (AChE; EC 3.1.1.7) activity recovery was evaluated in the whole brain and diaphragm tissues of mice pretreated with THA (5 mg/kg) and physostigmine (0.1 mg/kg) 15 min before poisoning with DFP (8 mg/kg). At 10 min after DFP administration residual AChE activity in the brain averaged 4, 25 and 15% of that in controls in the animals pretreated with atropine alone, atropine plus THA or atropine plus physostigmine, respectively. At 24 h after poisoning, brain AChE activity averaged 34 and 47% of that in controls in the mice protected by THA and physostigmine, respectively. As for the diaphragm, AChE activity in THA-pretreated animals was 29% of controls 10 min after poisoning versus 8 and 23% in unprotected and physostigmine-pretreated animals, respectively. At 24 h after poisoning, diaphragm AChE activities averaged 56 and 53% of controls in THA- and physostigminetreated animals, respectively. From these experiments it is concluded that THA exerts a considerable protective action against acute DFP-poisoning in the mouse, presumably by protecting neuronal AChE from irreversible inactivation by this organophosphorus agent.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01968968
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