Abstract
Dibenamine, Dibenzyline, two adrenergically inactive mono-β-chloroethylamines and a nitrogen mustard were found to react readily in vitro with sulfhydryl groups. In contrast to Dibenamine and Dibenzyline the three adrenergically inactive compounds did not react as completely in unbuffered media as in buffered media. A Dibenamine-cysteine product was isolated.
Data on the effects of Dibenzyline on liver sulfhydryl in vivo were equivocal. However, the molar disparity between the amount of drug tolerated and the total body sulfhydryl precluded obtaining meaningful data. Dibenamine reacted readily with both free and fixed liver sulfhydryl in vitro.
All five drugs were found to react in vitro with fifteen amino compounds and to form esters with fourteen carboxyl compounds, but the reactions were not as complete as with sulfhydryl. Reactions with phosphates and carbohydrateswere slight or absent.
Various of the drugs were found to react with amino and carboxyl groups of bovine serum albumin and with carboxyl groups of zein. The biological activities of insulin and Pitressin and the oxygen-carrying capacity of hemoglobin were reduced by Dibenamine.
Problems relating to the mechanism of action of Dibenamine and a possible chemical-biological correlation are discussed. It is concluded that alkylation of sulfhydryl by Dibenamine and its congeners provides a generally satisfactory mechanism for the production of adrenergic blockade.
Footnotes
- Received July 12, 1954.
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