Title
Protection of guinea pigs against soman poisoning by pretreatment with p-nitrophenyl phosphoramidates
Author
TNO Prins Maurits Laboratorium
Langenberg, J.P.
de Jong, L.P.A.
Benschop, H.P.
Publication year
1996
Abstract
Several p-nitrophenyl phosphoramidates with the general formula RO(NH2)P(O)OC6H4-p-NO2, in which R = CH2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2CH2CH2CH3, and CH2CH2Cl, as well as (NH2)2P(O)OC6H4-p-NO2 were administered intravenously to guinea pigs as pretreatment compounds for protection against the lethal effects of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) poisoning. Administration of phosphoramidates at a dose that produces 30% acetylcholinesterase (AChE) inhibition in the blood of atropinized guinea pigs at the moment of soman poisoning increases the subcutaneous LD50 of soman up to almost fivefold depending on which compound was used. A synergistic effect with atropine was observed. Three of these compounds offered a higher degree of protection against soman poisoning than pyridostigmine. Furthermore, the surviving animals pretreated with the two phosphoramidates that provided the highest protective ratio were in a better condition at 24 hr after soman intoxication than those pretreated with pyridostigmine. Due to the limited number of compounds and their different characteristics, it appeared difficult to demonstrate a relationship between the rate of spontaneous reactivation of AChE inhibited by the pretreatment compound and the protection against soman. Nevertheless, the results indicate that a several-fold decrease in the rate of spontaneous reactivation relative to that of pyridostigmine may increase the protective ratio against soman.
Subject
Protection
Guinea pigs
GB agent
Thyroid neoplasms
Nerve agents
Acetylcholinesterase, EC 3.1.1.7
Antidotes
Cholinesterase inhibitors
Nitrophenols
O-ethyl O-4-nitrophenyl phosphoramidate, 119401-65-9
Organophosphorus compounds
Soman, 96-64-0
Atropine
Phosphoramidic acid derivative
Pyridostigmine
Anesthesia
Animal experiment
Animal tissue
Enzyme inhibition
Intoxication
Intravenous drug administration
Lethality
Dose-Response Relationship, Drug
Half-Life
Animalia
Cavia porcellus
Sus scrofa
To reference this document use:
http://resolver.tudelft.nl/uuid:68035529-7dbd-460a-ab30-da23dacedf6f
DOI
https://doi.org/10.1006/taap.1996.0241
TNO identifier
128261
ISSN
0041-008X
Source
Toxicology and Applied Pharmacology, 140 (140), 444-450
Document type
article