2-Pralidoxime chloride

Patent 3,414,577 December 3,1968 assigned to Boehringer Ingelheim G.m.b.H. (Germany) 

Therapeutic Function Cholinesterase reactivator (antidote for nerve gas) Chemical Name 2-[(Hydroxyimino)methyl] -1-methylpyridinium chloride Common Name 2-PAM chloride Structural Formula  

Dimethyl sulfate Methyl chloride Sodium hydroxide 

As described in U.S. Patent 3,123,613, the preparation of the intermediate product, 2-pyridineaidoxime methomethylsulfate, Is as follows. 1 kg of 2-pyridinealdoxime is dissolved in 6 liters of acetone and filtered until clear. 2 kg (2 equivalents) of freshly distilled dimethyl sulfate are added and the solution mixed. In about 30 minutes crystals start to appear, after which a cooling bath is used to keep the temperature at about 30° to 35°C until the reaction is nearly complete (about 2 hours). 

The mixture is allowed to stand at room temperature overnight, the crystals filtered off and washed on a filter with acetone. The product Is obtained as colorless needles, which melt at 111° to 112.5°C. The methylsulfate is not stable indefinitely. For preparation of pure chloride salt it is desirable to use methylsulfate which gives no titratable acidity with sodium hydroxide using bromophenol blue as indicator. 

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Pralidoxime chloride Timepidium bromide Dimethyl sulfide... 

PAM chloride - 2-pralidoxime chloride. See oxime, parasympathetic nervous system -the part of the autonomic nervous system that decreases pupil size, heart rate, and blood pressure and increases functions, such as secretion of saliva, tears, and perspiration. 

Inhalation and dermal absorption Atropine (2 mg) IV repeat q 5 min, titrate until effective, average dose 6 to >f5 mg -use IM in the held before IV access (establish airway for oxygenation). Pralidoxime chloride (2-PAMC1) 600-f800 mg IM or 1.0 g IV over 20-30 min (maximum 2 g IM or IV per hour). 

Ventilate the patient. There may be an increase in airway resistance due to constriction of the airway and the presence of secretions. If breathing is difficult, administer oxygen. As soon as possible administer of atropine alone or in combination with pralidoxime chloride (2-PAMC1) or other appropriate oxime. Diazepam may be required to prevent or control severe convulsions. If diazepam is not administered within 40-minutes postexposure, then its effectiveness at controlling seizures is minimal. 

For humans, famphur is considered harmful or fatal if swallowed or absorbed through the skin, especially by children. If poisoning should occur, physicians are advised that atropine is antidotal and that pralidoxime chloride may be effective as an adjunct to atropine. Pour-on formulations are flammable, and users should keep them away from heat, sparks, and open flames including hot branding irons and cautery dehorning devices (American Cyanamid Company 1984). 

Nerve Agent Antidote Kit (NAAK or MARK I) consists of an atropine auto-injector (2 mg), a pralidoxime chloride auto-injector (2-Pam-Cl, 600 mg), the plastic clip joining the two injectors, and a foam case. The kit serve as a countermeasure to nerve agents, including tabun (GA), sarin (GB), soman (GD), GF, and VX. Military personnel can receive three MARK I for self/buddy aid. Possible side effects of atropine and/or 2-PAM-C1 are deemed insignificant in a nerve agent casualty. Intravenous atropine and 2-PAM-C1 can also be made available. The MARK I kit is manufactured by Survival Technology, Inc., Rockville, Maryland. 

PAM Chloride Trade names protopam chloride, or pralidoxime chloride. 2-PAM chloride can be used in the treatment of nerve agent poisoning. 

If the poisoning is due to an organophosphate, prompt administration of pralidoxime chloride will result in dephosphorylation of cholinesterases in the periphery and a decrease in the degree of the blockade at the skeletal neuromuscular junction. Since pralidoxime is a quaternary amine, it will not enter the CNS and therefore cannot reactivate central cholinesterases. In addition, pralidoxime is effective only if there has been no aging of the phosphorylated enzyme. Pralidoxime has a greater effect at the skeletal neuromuscular junction than at autonomic effector sites. 

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