2- pyridine aldoxime methiodide toxicity

Irreversible anticholinesterases include the organophosphorus inhibitors and ambenonium, which irreversibly phosphorylate the esteratic site. Such drugs have few clinical uses but have been developed as insecticides and nerve gases. Besides blocking the muscarinic receptors with atropine sulphate in an attempt to reduce the toxic effects that result from an accumulation of acetylcholine, the only specific treatment for organopho-sphate poisoning would appear to be the administration of 2-pyridine aldoxime methiodide, which increases the rate of dissociation of the organophosphate from the esteratic site on the enzyme surface. 

A successful antidote to organophosphorus compounds must hydrolyze the enzyme-phosphoryl bond to release the acetylcholinesterase. The simplest compound that will do this is hydroxylamine. Unfortunately, hydroxylamine is toxic at the concentrations needed. However, derivatives can be prepared that work at much lower concentrations and can be used clinically. One such derivative is pyridine aldoxime methiodide (Fig. 8.7). In this derivative, the hydroxylamine group is fixed in position relative to the pyridine ring. The pyri-... 

Reactivation is possible by treatment with hydroxylamine which removes the attached phospho-ryl group. The latter compound is, however, toxic in the concentration which would be required. Pyridine aldoxime methiodide (PAM) (12.152) is an effective antidote. PAM at 10 M is as effective as NH2OH at 1 M concentration. 

Jager, B.V., and Stagg, G.N. Toxicity of diacetyl monoxime and of pyridine-2-aldoxime methiodide in man. Bull. Johns Hopkins Hosp. 102 203-211, 1958. 

Its excellent pesticidal properties are vitiated by its high toxicity to mammals. Its acute oral lDj, for rats is S.4 mg/kg. In chronic oral toxicity tests the no lTect level for rats was found to be SO ppm. Atropine sulfate appeared to be an antidote of oxamil, but pyridine-2-aldoxime methiodide (PAM), a well-known antidote to cholinesterase inhibitors, does not appear to be effective in this respect. 

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