Metabolism of the anti-depressant lortalamine

  title={Metabolism of the anti-depressant lortalamine},
  author={L. F. Elsom and S. R. Biggs and Leslie F Chasseaud and David R. Hawkins and J. R. Pulsford and Austin Darragh},
  journal={European Journal of Drug Metabolism and Pharmacokinetics},
SummaryHumans excreted an oral dose of 5 mg of the anti-depressant lortalamine (radiolabelled with carbon-14) mainly in the urine (98% during 5 days).Plasmal 4C concentrations were highest (about 44 ng equiv./ml) between 1.5–3 h when the corresponding concentrations of unchanged drug were about 17 ng/ml. Unchanged drug concentrations appeared to decline with a half-life of about 5 h. Concentrations of14C then declined rapidly and were below the limits of detection (12 ng equiv./ml) at 24–36 h… 


Metabolism of diazepam in rat, dog, and man.
Diazepam, 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H- 1,4-benzodiazepin-2-one, synthesized and administered to rats, dogs and 2 human subjects revealed that the highest levels of radioactivity were in the liver and perirenal fat, while the lowest concentration of H3 was in the brain.
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Knowing of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications, which contribute to both the therapeutic and the adverse effects of these compounds.
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Radioactivity was excreted mainly in the urine of man, miniature swine and rhesus monkey, but in the faeces of rat and dog, and mass-spectrometric analysis of several metabolites indicated N-demethylation and oxidation of the alicylic ring or a combination of both pathways.
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The N-demethylated metabolite (LM 1580), which has a pharmacological activity nearly identical to that of LM 1404, was very abundant in plasma of both species, with half-lives of 13 hr in dogs and 3.5 hr in rats.
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