Abstract

Equal amounts of unlabeled and dideuterium-¹⁵N-labeled nortriptyline were given to blood-perfused dog heart-lung, isolated hung and isolated heart preparations and to incubates of homogenized heart and lung tissues. Metabolism of time drug was studied by gas chromatography-mass fragmentography with the artificially created mass spectral doublet to indicate the presence of parent drug and metabolites. Desmethylnortriptyline was identified in heart, lung and erythrocytes of the heart-lung preparation, in lung from the isolated lung preparations and in incubated lung homogenate. but not in the isolated heart preparations or in the incubated heart homogenate. These results indicate that the lung is capable of demethylating nortriptyline. In addition, it was noted that the heart concentrates both the metabolite and the parent drug; this observation may be significant in view of the reported cardiac toxicity of nortriptyline.