2- pyridine aldoxime methiodide

Reactivators of phosphorylated ChE. Pyridine aldoxime methiodide (PAM) and related compounds are the best known. They reactivate the phosphorylated enzyme so long as aging has not occurred. They do not, however, reactivate the aged enzyme. ChE which has been phosphorylated by certain nerve gases ages rapidly ... 

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. 

Treatment for Parathion poisoning has been improved by the availability of the oxime 2-PAM (2-pyridine aldoxime methiodide) (ref. 

Synonyms. PAM P-2-AM 2-PAM Iodide 2-PAMI Pamium Pyraloxime Iodide 2-Pyridine Aldoxime Methiodide. 

Pyridine aldoxime methiodide, 915 Pyridine aldoxime methochloride, 915 Pyridine aldoxime methyl mesylate, 915 Pyridinecarboxamide, 807 Pyridinecarboxylic acid, 808 Pyridinemethanol, 809... 

In 1955, Wilson and Ginsburg in the United States and Childs et al. in the United Kingdom researched and published independently on the efficacy of the compound 2-pyridine aldoxime methiodide (2-PAM) as a reactivator of phospho-rylated cholinesterases. The next compound of interest was trimedoxime, which was synthesized... 

Figure 23. The reactivation of alkylphosphate-inhibited cholinesterase by 2-pyridine aldoxime methiodide (18)...

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-... 

Pyridine aldoxime methiodide. The active portion, shown with purple bonds, of this antidote is analogous to hydroxylamine. 

How does pyridine aldoxime methiodide function as an antidote for organophosphate poisoning ... 

Organophosphates inactivate acetylcholinesterase by binding covalently to it. Since acetylcholine is not broken down, nerve transmission continues, resulting in muscle spasm. Pyridine aldoxime methiodide (PAM) is an antidote to organophosphate poisoning because it displaces the organophosphate, thereby allowing acetycholinesterase to function. 

Quinby GE, Loomis TA, Brown HW. Oral occupational parathion poisoning treated with 2-PAM iodide (2-pyridine aldoxime methiodide). N Engl J Med. 1963 268 639-643. 

Funckes AJ. Treatment of severe parathion poisoning with 2-pyridine aldoxime methiodide (2-PAM). Arch Environ Health. 1960 1 404-406. 

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. 

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