Effects of Diazepam On Soman-Induced Lethality, Convulsions, And Performance Deficit

Murphy, Michael R.; Blick, Dennis W.; Fanton, John W.; Miller, Stephanie A.; Kerenyi, Sandra Z.; Weathersby, Frank R.; Brown, G. Carroll; Hartgraves, Stanley L.

doi:10.1037/e535592006-001

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“…2,2-Diphenylpropionic acid (5, 3.0 g) was dispersed in freshly distilled thionyl chloride (20 mL), and the mixture was refluxed for 2 h. The thionyl chloride was removed under vacuum, and the residue was dissolved in n-hexane and filtered, and the solvent was evaporated to leave 3.0 g of colorless oil. 3-Hydroxy-2-(2′,2′-diphenylpropionoxymethyl)pyridine (7). A solution of the acid chloride 6 (1.22 g, 0.005 mol) in dry benzene (10 mL) was added to a solution of 3-hydroxy-2-(hydroxymethyl)pyridine hydrochloride (0.9 g, 0.006 mol) in dry pyridine (30 mL).…”

Section: -Hydroxypyridine (3) and 2-[[(dimethylamino)carbonyl]-oxy]mentioning

confidence: 99%

“…Current prophylactic and therapeutic regimens for the protection against organophosphate (OP) poisoning include a pretreatment regimen consisting of (i) pyridostigmine, the reversible, covalent acetylcholinesterase (EC 3.1.1.7; AChE) inhibitor, − (ii) the muscarinic receptor antagonist atropine (ATR), and (iii) the AChE reactivator pralidoxime chloride. , Additional treatment with diazepam has proven advantageous in attempts to prevent convulsions. − These regimens provide extensive protection against OP intoxication in animals. However, treatment might be considerably simplified if drugs that possessed multiple protective functions were used.…”

Section: Introductionmentioning

confidence: 99%

“…3,6 Additional treatment with diazepam has proven advantageous in attempts to prevent convulsions. [7][8][9] These regimens provide extensive protection against OP intoxication in animals. However, treatment might be considerably simplified if drugs that possessed multiple protective functions were used.…”

Section: Introductionmentioning

confidence: 99%

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Pyridophens: Binary Pyridostigmine−Aprophen Prodrugs with Differential Inhibition of Acetylcholinesterase, Butyrylcholinesterase, and Muscarinic Receptors

et al. 2002

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A series of "binary prodrugs" called carbaphens,(1) carbamylated derivatives on one or both of the aromatic rings of the muscarinic receptor antagonist aprophen [(N,N-diethylamino)ethyl 2,2-diphenylpropionate], were synthesized to develop binary prophylactic agents against organophosphorus intoxication. As a group, the carbaphens retained the muscarinic receptor antagonist properties of aprophen but also preferentially inhibited butyrylcholinesterase (BChE) in contrast to acetylcholinesterase (AChE). Therefore, a new series of compounds named pyridophens were designed and synthesized to achieve binary prodrugs to preferentially inhibit AChE over BChE, while still retaining the muscarinic receptor antagonism of aprophen. The pyridophens consist of the basic pyridostigmine skeleton combined with the 2,2-diphenylpropionate portion of aprophen by replacement of the diethylamino group. Three compounds, 9 (a tertiary pyridine), 10 (a quaternary pyridine), and 12 (a tertiary tetrahydropyridine), were found to be effective inhibitors of both BChE and AChE. However, 10, N-methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2'2'-diphenylpropionoxy-methyl)pyridinium iodide, inhibited AChE selectively over BChE, with a bimolecular rate constant similar to pyridostigmine. In contrast to their potent cholinesterase inhibitory activity, all of the pyridophen analogues were less potent antagonists of the muscarinic receptor than aprophen.

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Section: -Hydroxypyridine (3) and 2-[[(dimethylamino)carbonyl]-oxy]mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pyridophens: Binary Pyridostigmine−Aprophen Prodrugs with Differential Inhibition of Acetylcholinesterase, Butyrylcholinesterase, and Muscarinic Receptors

et al. 2002

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Effects of Diazepam On Soman-Induced Lethality, Convulsions, And Performance Deficit

Cited by 1 publication

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Pyridophens: Binary Pyridostigmine−Aprophen Prodrugs with Differential Inhibition of Acetylcholinesterase, Butyrylcholinesterase, and Muscarinic Receptors

Pyridophens: Binary Pyridostigmine−Aprophen Prodrugs with Differential Inhibition of Acetylcholinesterase, Butyrylcholinesterase, and Muscarinic Receptors

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