PT  - JOURNAL ARTICLE
AU  - Brodie, B. B.
AU  - Aronow, Lewis
AU  - Axelrod, Julius
TI  - THE FATE OF DIBENZYLINE IN THE BODY AND THE ROLE OF FAT IN ITS DURATION OF ACTION
DP  - 1954 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 21--29
VI  - 111
IP  - 1
4099  - http://jpet.aspetjournals.org/content/111/1/21.short
4100  - http://jpet.aspetjournals.org/content/111/1/21.full
SO  - J Pharmacol Exp Ther1954 May 01; 111
AB  - Methods are described for the estimation of Dibenzyline and its metabolite, N-phenoxyisopropyl-N-benzyl amine, in biological material. After intravenous administration in the dog, Dibenzyline is in part rapidly metabolized and in part localized in fat where it is stable and from which it slowly diffuses into the bloodstream. The degree of adrenergic blocking activity is related to the concentration of the drug in fat. Studies with C14 labelled Dibenzyline show that there are definite though small concentrations of drug in plasma during the time that the effects of the drug are exerted. After oral administration about four times as much Diberizyline as Dibenamine is found in body fat. The oral efficacy of Dibenzyline may be related to its high fat solubility. A major pathway of biotransformation of Dibenzyline involves dealkylation to yield N-phenoxyisopropyl-N-benzyl amine. No evidence that Dibenzyline is hydrolyzed in vivo to yield the corresponding alcohol was found. The observations presented in this paper suggest that it is unnecessary to postulate that Dibenzyline and other adrenergic blocking agents of the Dibenamine type act irreversibly on a cell receptor.