Qualitative metabolic fate of phenoxybenzamine in rat, dog, and man. use of 15N-labeling
Knapp, D.R.; Holcombe, N.H.; Krueger, S.A.; Privitera, P.J.
Drug Metabolism and Disposition the Biological Fate of Chemicals 4(2): 164-168
1976
ISSN/ISBN: 0090-9556 PMID: 5261 Document Number: 98878
Administration of an equimolar mixture of unlabeled and 15N-labeled phenoxybenzamine to rats and dogs facilitated identification of urinary metabolites by gas chromatography/chemical-ionization mass spectrometry by virtue of the the conspicuous equal-intensity ion pairs produced. By use of this technique N-benzyl-N-phenoxyisopropylamine (III), N-benzyl-N-(p-hydroxy-phenoxyisopropyl)amine (IV), and 2-benzylamino-1-propanol (VI) were identified as metabolites in rats. Phenoxyisopropylamine (V) as well as III and IV were identified in dogs. Compound IV was identified in humans under clinical treatment with phenoxybenzamine. The metabolites were screened for cardiovascular activity in rats. Compound III had weak alpha-adrenergic blocking activity and V elicited a hypertensive response.