Pyridine methochloride

Pyridine methochloride is converted by aqueous alkali and a mild oxidizing agent (ferricyanide) to a solid compound of formula C6H7NO, which shows no hydroxyl absorption in the infrared. What is a likely structure for this substance and how is it formed Would you expect a similar reaction with pyridine ... 

Sidell, F.R., Groff, W.A., and Ellin, R.I. Blood levels of oxime and symptoms in humans after single and mutliple oral doses of 2-pyridine aldoxime methochloride. J. Pharm. Scl. 58 1093-1098, 1969. 

Treatment of test animals with anticholinesterase agents such as atropine and 2-PAM significantly reduced the acute lethality of diazinon in rats indicating that acute diazinon lethality is primarily attributable to the inhibition of acetylcholinesterase. Administration of 16 mg/kg atropine intramuscularly, with or without 30 mg/kg pyridine 2-aldoxime methochloride (2-PAM) given either orally or intravenously or both, to female albino rats 10 minutes before diazinon exposure increased the LD50 value (294 mg/kg) for diazinon for this species by a factor of 3.2 (with 2-PAM) or 1.7 (without 2-PAM) (Harris et al. 1969). 

It is also important to mention the use of the reactivation of the acetylcholinesterase by pyridine-2-aldoxime methochloride to discriminate between the toxin and potential insecticides [96]. Once phos-phorylated, the active site serine of the enzyme can be reactivated by powerful nucleophilic agents such as oximes. However, this reactivation is not possible if attempted too late due to the stable adduct formed by the dealkylation (aging) of the inhibitor s remaining group. When acetylcholinesterase is inhibited by anatoxin-a(s), it shows immediately the characteristics of an aged enzyme and cannot be reactivated. In this way, it is possible to distinguish between the inhibition caused by anatoxin-a(s) and the one provoked by other insecticides. 

Pyridine-2-aldoxime methochloride 345 Pyrogallol, catechol, phenol and p-cresol 363... 

Synonyms. 2-PAM Chloride 2-PAMCl Pyraloxime Chloride 2-Pyridine Aldoxime Methochloride. 

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

The standard treatment of nerve agent-induced muscle toxicity calls for (1) reactivation of the phosphorylated AChE with an oxime, and (2) blockage of the nicotinic ACh receptor sites from the stimulating action of ACh with fii-tubocurarine. Oximes such as obidoxime, pralidoxime (2-pyridine aldoxime methochloride, 2-PAM) and a few others have been found very effective when given in combination with other drugs such as atropine, pretreatment with oximes varies with the ehemieal structures of the nerve agents and depends on the time after exposure. For example, it has been... 

Standard post-exposure treatments include eoneurrent administration of anticholinergics, such as the musearinie cholinergic blocker atropine sulfate, and AChE reactivators, such as obidoxime and pyridine-2-aldoxime methochloride (also known as 2-PAM). Oximes cannot reactivate OP-inhibited AChE that has already aged . Therefore, traditional oxime treatment is considered to be less effective for those agents such as soman, for which aging is rapid (Worek et al, 2005). 

Murtha, E.F. and Harris, L.W., Effects of 2-pyridine aldoxime methochloride on cerebral acetylcholinesterase activity and respiration in cats poisoned with sarin, Life Sci., 27, 1869, 1980. 

Onda has given complete detailson his conversion of the protopinoid alkaloid allocryptopine to chelerythrine (see Scheme 21.3). The critical step was the photolysis of anhydroallocryptopine to yield an unstable base, probably 8, which readily isomerized to tetrahydrochelerythrine. An alternate route to the required starting material, dihydroberberine methochloride, involves sodium borohydride in pyridine reduction of berberine to dihydroberberine, followed by quaternization with dimethyl sulfate. ... 

Antidotes. Because the acute toxicity to man of many of the phosphorus insecticides is high, first-aid remedies are kept on hand. The most useful of these is an injection of atropine (which acts primarily on muscarinic sites) followed by an oxime specific for nicotinic sites. These oximes reactivate phosphorylated acetylcholinesterase in patients (Holmes and Robins, 1955) just as with the isolated enzyme (Wilson and Meislich, 1953). This reaction involves a competition, between the hydroxyl-groups of serine and of the hydroxylamine, for the phsphoryl-group. The covalent bond with the serine is broken, and simultaneously a new covalent bond formed with the hydroxylamine (see Scheme 12.1). One of the best reactivators is pralidoxime 12.27) (2-PAM), which is the anti form of pyridine-2-aldoxime methochloride. Widely differing doses of antidote are required, depending on the strength of the phosphate-enzyme bond, which varies with the nature of the insecticide. 

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