ABSTRACT
In an attempt to develop effective antidote against organophosphorus intoxication, some new imidazole-pyridinium mono-oximes, long chain pyridinium mono-oximes and cholineacetyltransferase inhibitors were synthesised. These compounds were evaluated for their in vivo therapeutic protection and neuromuscular function studies in rodents. The results indicate that SPK-series oximes may be useful against sarin poisoning without any beneficial effect against VX (O-Ethyl S-2-NN-diisopropylaminoethyl methylphosphonofluoridate) intoxication. The cholineacetyltransferase (ChAT) inhibitors may not be of any help against any of the OP compounds studied in this study.
Subject(s)
Animals , Antidotes/chemical synthesis , Choline O-Acetyltransferase/antagonists & inhibitors , Cholinesterase Inhibitors/toxicity , Enzyme Inhibitors/chemical synthesis , Lethal Dose 50 , Male , Mice , Neuromuscular Junction/drug effects , Organophosphorus Compounds/antagonists & inhibitors , Organothiophosphorus Compounds/toxicity , Oximes/chemical synthesis , Pyridinium Compounds/chemical synthesis , Rats , Rats, Wistar , Sarin/toxicityABSTRACT
Subacute dose of 0,0-diisopropyl phosphorofluoridate (DFP), a potent organophosphorus ester capable of producing delayed neurotoxicity (OPIDN), did not produce any significant change in the levels of lysosomal and mitochondrial marker enzymes of brain, liver and serum at any time after treatment in hens protected with atropine. The results suggest the absence of any involvement of mitochondrial and lysosomal enzymes at any stage in the development of OPIDN in susceptible species by treating with DFP.