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- W1956551469 abstract "Important anticholinesterase activity has been demonstrated with N, N-bis(2-diethylaminoethyl)oxamide bis-2-chlorobenzyl chloride (WIN 8077). This action is highly specific for acetylcholinesterase. The 2-methoxybenzyl analog (WIN 8078) is a weak inhibitor of acetylcholinesterase.WIN 8077 increases contraction height of the cat sciatic nerve-gastrocnemius muscle preparation after intravenous administration of doses as small as 6.0 microgm./kgm. WIN 8078 has little or no potentiating action.Both WIN 8077 and WIN 8078 (2.9 and 11.2 microgm./kgm., respectively, cat) are effective antagonists of d-tubocurarine (also in the dog and mouse), facilitate indirect excitation of skeletal muscle and potentiate and sensitize transmission in the autonomic nervous system.These compounds are effective antagonists of tetraethylpyrophosphate in the mouse.The above effects are obtained with doses of WIN 8077 and WIN 8078 that produce only small or undetectable inhibition of acetylcholinesterase in vivo (blood, muscle and brain).Acute lethal effects of the oxamide compounds are associated with respiratory depression which results from either central or peripheral (curariform) action at the neuromyal junction.The significance of these findings is discussed. The data obtained suggest that WIN 8077 and WIN 8078 favor excitation at transmission sites either by direct action on the receptor mechanism or by an effect on some enzyme system other than acetylcholinesterase." @default.
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- W1956551469 date "1955-10-01" @default.
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- W1956551469 title "An evaluation of the pharmacologic actions of some bis-quaternary salts of basically substituted oxamides (WIN 8077 and analogs)." @default.
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