2-PAM Iodide

Referred to ChR of the first generation (the development started in the middle 60-ies of the last century) are pralidoxime (2-PAM-iodide... 

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

Pralidoxime administered to human volunteers at a dose of lOmg/kg by intramuscular route produced a plasma concentration of >4 mg/1 within 5-10 min and maintained levels above this threshold for an hour (Sidell and Groff, 1971). Adverse effects of 2-PAM iodide in volunteers include dizziness, blurred vision, occasional diplopia, impaired accommodation, nausea, and headache (Jager and Stagg, 1958 Sidell and Groff, 1971). 

SYNS 2-FORMYL-l-METHYLPYRIDINIUM IODIDE OXIME 2-FORMYL-N-METHYLPYRIDINIUM OXIME IODIDE 2-HYDROXYIMINOMETHYL-l-METHYLPYRIDINIUM IODIDE l-METHYL-2-ALDOXIMINOPYRIDINTUM IODIDE l-METHYL-2-HYDROXYIMINOMETHYLPYRIDINIUM IODIDE N-METHYLPYRIDINE-2-ALDOXIME IODIDE N-METHYLPYRIDINIUM-2-ALDOXIME IODIDE NSC-7760 PAM (CZECH) 2-PAM IODIDE PRALIDOX-... 

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. 

The clinical experience with the use of 2-PAM iodide, given with atropine and diazepam, in the treatment of the victims of Tokyo sarin attack in 1995 was very favorable (Sidell et al., 2009). However, 2-PAM should not be recommended as the drug of choice for the management of poisoning with all OPs due to its lack of efficacy against tabun and soman. 

Other salts of N-methylpyridinium-2-formyl oxime are identified by the abbreviation 2-PAH followed by the common symbols for elemental anions (such as 2-PAM I for the iodide) or the names of organic anions (such as 2-PAM tartrate). Other salts of N.N -trimethyl-ene-bis (4-formylpyridinlum oxime) are identified by appending the designation for the anion to the abbreviation TMB-4. 

In the rat, absorption of III from a single-loop intestinal preparation during 1 h was found to be only about 13% of that of 2-PAM 1.37 The rate of absorption of I was somewhat lower than that of the iodide II was absorbed at nearly the same rate as the iodide.38 Three hours after the oximes were put into intestinal loops, slightly more than one-third as much of III had been absorbed as of 2-PAM I. 

Kondrltzer et al.,130 n searching for a salt of 2-PAM that would be more soluble than 2-PAM I in water, made a number of other salts. Most of these were considerably more soluble in water than 2-PAM I. One of the most soluble was the lactate, with a solubility of 1 g/ml. Unfortunately, this salt was found to be quite unstable in aqueous solution with respect to heat. I was less soluble in water than the lactate, but more than 13 times as soluble as the iodide. Furthermore, solutions of I at a pH of 3.5-4.3 could be autoclaved at 120°C for 15 min with only a 4% loss. Solutions of this salt stored at 50-70°C for 1-3 mo contained at least 78% of the original oxime and no more than 0.1% of hydrogen cyanide. When the aged solutions were examined for lethality to experimental animals, their lethal activities were exactly those expected on the basis of their oxime concent rat ions. 

The biologic half-lives of the five salts of 2-PAM calculated from both the data on plasma concentrations at various times after Ingestion and those on urinary excretion are given in Table 4. The table demonstrates that the iodide was cleared from the plasma more slowly than the other salts and that the dihydrogen phosphate was cleared from the plasma a little more rapidly than the others. 

Kaiser, S.C. 1959. Metabolism of 2-formyl-l-methyl pyrldlnlum Iodide oxime (2-PAM). CWLR 2347. 

D-l 2170 2-PAM pralidoxime chloride (or Iodide) protopam chloride (or iodide) 2-f ormyl-N-me thylpyridinium chloride Tor iodide) oxime pyrld ine-2-aldoxime methochloride (or methlodlde) 51-15-0 607... 

Sakurada, K., Matsubara, K., Sbimizu, K., Shiono, H., Seto, Y., Tsuge, K., Yosbino, M., Sakai, I., Mukoyama H., Takatori., T. (2003). Pralidoxime iodide (2-PAM) penetrates accross the blood-brain barrier. Neurochem. Res. 28 1401-7. 

Pralidoxime iodide, CyH IN-O, 2-pyridine aldoxime me th-iedide, 2-PAM, Pmtopam iodide. Yellow crystals from alcohol. mp 225-226. Soly at 25 48 mg /ml. Very sol in water, fairly sol in hot alcohol, poorly sol in cold alcohol. Insol in ether, acetone. LD in mice (mg/kg) 140-178 i.v.,... 

Since l-n-dodecyl-3-(hydroxyiminomethyl)pyridinium iodide was indicated to be a more effective nucleophilic reagent for the hydrolysis of organophosphorus compounds, it was examined in addition to 2-PAM, 2-PAD, histidine hydrochloride, and succinyl choline as possible coatings (55,56). Among these, 3-PAD was found to be the best coating for compounds with the G agent structure, and histidine hydrochloride for compounds of the malathion type. Table 3. 

The 2-cyano-N-methylpyridinium ion, the 2-carboxy-l-methylpyridinium ion and N-methyl-2-pyridone have been identified as metabolites of V-methylpyri-dinium-2-aldoxime iodide (2-PAM) (Xn-413) in rats. 

Recommended doses of atropine are 2 mg in patients with mild symptoms that are primarily ocular, but without respiratory symptoms or seizures 4 mg in patients with moderate symptoms, including respiratory symptoms such as dyspnea and 6 mg in patients with severe symptoms, including seizures and respiratory arrest. The standard administration route should be intramuscular. As menhoned previously, intravenous administration of atropine in the treatment of severe symptoms such as hypoxemia can induce ventricular fibrillation thus, intramuscular administration is advised. Oxime agents such as 2-pralidoxime methiodide (2-PAM), or 2-formyl-l-methylpyridinium iodide oxime should also be given. The recommended dose for 2-PAM in... 

In 1988, Linstrumelle and Huynh used an all-palladium route to construct PAM 4 [21]. Reaction of 1,2-dibromobenzene with 2-methyl-3-butyn-2-ol in triethylamine at 60 °C afforded the monosubstituted product in 63 % yield along with 3% of the disubstituted material (Scheme 6). Alcohol 15 was then treated with aqueous sodium hydroxide and tetrakis(triphenylphosphine)palladium-copper(I) iodide catalysts under phase-transfer conditions, generating the terminal phenylacetylene in situ, which cyclotrimerized in 36% yield. Although there was no mention of the formation of higher cyclooligomers, it is likely that this reaction did produce these larger species, as is typically seen in Stephens-Castro coupling reactions [22]. 

In order to minimize the formation of side products, PAM 4 can be assembled via an intramolecular approach [23]. The Sonogashira protocol [15] and conversion of masked iodides [24] comprises most of the chemistry involved in Scheme 7. Using these proven methods, diyne 16 and subsequently triyne 17 can be prepared quickly. lodination, desilylation, and intramolecular alkynylation with Pd(dba)2 under high dilution conditions furnished 4 as the sole product. 

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