pralidoxime and methanesulfonic-acid

This study compared the ability of nine oximes (HI-6, HLö7, MMB-4, TMB-4, carboxime, ICD585, ICD692, ICD3805, and 2-PAM) to reactivate in vivo cholinesterase (ChE) in blood, brain, and peripheral tissues in guinea pigs intoxicated by one of four organophosphorus nerve agents. Two bis-pyridinium compounds without an oxime group, SAD128 and ICD4157, served as non-oxime controls. Animals were injected subcutaneously with 1.0 x LD(50) of the nerve agents sarin, cyclosarin, VR or VX and treated intramuscularly 5 min later with one of these oximes. Toxic signs and lethality were monitored; tissue ChE activities were determined at 60 min after nerve agent. Some animals exposed to sarin or cyclosarin, with or without non-oxime treatment, died within 60 min; however, no animal treated with an oxime died. For VR or VX, all animals survived the 60 min after exposure, with or without non-oxime or oxime therapy. The four nerve agents caused differential degrees of inhibition in blood, brain regions and peripheral tissues. The tested oximes exhibited differential potency in reactivating nerve agent-inhibited ChE in various peripheral tissues, but did not affect ChE activity in the brain regions. There was no direct relation between blood and peripheral tissues in the reactivating efficacy of oxime treatments. ChE inhibited by sarin was the most susceptible to oxime reactivation while cyclosarin the least susceptible. There was no difference in the ChE reactivating potency between the dimethanesulfonate and dichloride salts of HI-6. MMB-4 significantly reactivated the ChE inhibited by these four nerve agents in blood and all three peripheral tissues of the guinea pig, and among all the oximes tested it was the most effective in vivo ChE reactivator against all four nerve agents.

Topics: Animals; Brain; Chemical Warfare Agents; Chlorides; Cholinesterase Reactivators; Cholinesterases; Databases, Factual; Diaphragm; Enzyme Activation; Erythrocytes; Guinea Pigs; Male; Mesylates; Muscle, Skeletal; Myocardium; Organ Specificity; Organophosphorus Compounds; Oximes; Pralidoxime Compounds; Salts; Solubility

Topics: Chemistry, Pharmaceutical; Cyanides; Hydrogen-Ion Concentration; Kinetics; Mesylates; Pharmacy; Pralidoxime Compounds; Pyridines; Research; Sulfonic Acids; Temperature

Topics: Animals; Atropine; Cholinesterase Inhibitors; Dogs; Hydroxylamines; Lactic Acid; Mesylates; Oximes; Phosphates; Pralidoxime Compounds; Pyridines; Sarin

The soluble methanesulphonate of the oxime 2-hydroxyiminomethyl-N-methylpyridinium (P2S) has been used to treat animals poisoned with sarin or ethyl pyrophosphate. The effect of the size of the dose, and its time of administration in relation to poisoning, have been examined. This oxime is very efficient in conjunction with atropine when given either before or after poisoning. About 30 mg./kg. seems to be the optimum therapeutic dose of the methanesulphonate. The significance of this optimum is discussed in relation to the treatment of accidental poisoning by organophosphate insecticides in man.

Topics: Animals; Atropine; Diphosphates; Humans; Insecticides; Male; Mesylates; Organophosphate Poisoning; Oximes; Phosphates; Pralidoxime Compounds; Pyrans; Pyridinium Compounds; Sarin

Topics: Antidotes; Mesylates; Organophosphate Poisoning; Pralidoxime Compounds; Pyridines; Pyridinium Compounds

The toxicity of 2-hydroxyiminomethyl-N-methylpyridinium methanesulphonate (P2S) has been determined in a number of species by various routes. It is approximately equally toxic in the rat, mouse, and guinea-pig. It is much more toxic in the dog. Atropine influences the toxicity of P2S differently in different species. From the results obtained attempts have been made to assess the maximum safe dose which can be given intramuscularly to man.

Topics: Animals; Dogs; Guinea Pigs; Humans; Male; Mesylates; Mice; Pralidoxime Compounds; Pyridines; Pyridinium Compounds; Rats