Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos.

Publisher: Blackwell Country of Publication: England NLM ID: 101208422 Publication Model: Print Cited Medium: Print ISSN: 1742-7835 (Print) Linking ISSN: 17427835 NLM ISO Abbreviation: Basic Clin Pharmacol Toxicol Subsets: MEDLINE

Publication: <2005-> : Oxford : Blackwell
Original Publication: Copenhagen, Denmark : Oxford, UK : Nordic Pharmacological Society Distributed by Blackwell Munksgaard, 2004-

Organophosphate Poisoning*; Dichlorvos/*poisoning ; Monocrotophos/*poisoning ; Trimedoxime/*therapeutic use; Acetylcholine/chemistry ; Acetylcholine/metabolism ; Animals ; Brain Chemistry/drug effects ; Carboxylesterase/antagonists & inhibitors ; Carboxylesterase/blood ; Carboxylesterase/drug effects ; Diaphragm/drug effects ; Diaphragm/physiology ; Dichlorvos/administration & dosage ; Dichlorvos/antagonists & inhibitors ; Drug Evaluation, Preclinical/methods ; Erythrocytes/chemistry ; Erythrocytes/drug effects ; Erythrocytes/physiology ; Injections, Intravenous ; Lethal Dose 50 ; Male ; Mice ; Monocrotophos/administration & dosage ; Monocrotophos/antagonists & inhibitors ; Organophosphorus Compounds/administration & dosage ; Organophosphorus Compounds/antagonists & inhibitors ; Oximes/administration & dosage ; Oximes/pharmacology ; Oximes/therapeutic use ; Time Factors ; Trimedoxime/administration & dosage ; Trimedoxime/pharmacokinetics

The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.

0 (Organophosphorus Compounds)
0 (Oximes)
56-97-3 (Trimedoxime)
6923-22-4 (Monocrotophos)
7U370BPS14 (Dichlorvos)
EC 3.1.1.1 (Carboxylesterase)
N9YNS0M02X (Acetylcholine)
RLZ2S71REI (heptenophos)

Date Created: 20050201 Date Completed: 20051018 Latest Revision: 20151119

20231215

10.1111/j.1742-7843.2005.pto960204.x

15679473