Abstract
A series of bisquaternary ammonium-biscyanohydrin compounds were found to be potent neuromuscular blocking agents of the tubocurarine type when assessed in the sciatic nerve-gastrocnemius muscle of the chicken and in the isolated phrenic nerve-diaphragm of the rat. When the cyano group was not present in the molecule, the potency decreased several fold. This phenomenon was greater with the unsubstituted alcohol than with the acetyl or benzoyl derivatives. Presumably, it was due to the interference of the latter radicals with the liberation of cyanide from the molecule. Sodium nitrite did not modify the toxicity of the cyanohydrin, but sodium thiosulfate, hydroxocobalamin and their combination were antagonistic. Titrimetric studies revealed that cyanide is released in vitro. The presence of an amine in the cyanohydrin solution greatly increased the amount of cyanide that was liberated. It was concluded that the increased potency observed in compounds possessing an easily-releasable cyanide was not owing completely to a configurational change introduced by the presence of the nitrile, but rather was the result of a localized release of hydrocyanic acid.
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