THE CHEMICAL TRANSFORMATIONS OF DIBENAMINE AND DIBENZYLINE AND BIOLOGICAL ACTIVITY

¹ Department of Pharmacology, University of Utah College of Medicine, Salt Lake City
² Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, Michigan

1. The chemical transformations of Dibenamine, Dibenzyline and N,N-dicyclohexyl--chloroethylamine were studied.

2. All three compounds release chloride more rapidly than hydrogen ion. Dibenzyline releases chloride the fastest and Dibenamine the slowest of the three compounds. Chloride is released in a first order reaction; however, it is also postulated that some chloride is released in a second order reaction.

3. The energy of activation of the first order reaction is about 18,000 calories per mole under the conditions employed.

4. Partially transformed solutions react with more thiosulfate than can be accounted for by unreacted drug but with less than that predicted from the hydrogen ion released. It is concluded that an ethylenimonium intermediate is formed from each compound.

5. The adrenergic blocking activity of the calculated ethylenimonium of Dibenamine was tested and found to be approximately as potent as Dibenamine itself.

6. It is concluded that the kinetics of the transformations alone cannot account for the presence or absence of adrenergic blocking activity among the -haloalkylamines.