Metabolism of the anti-depressant lortalamine

Humans excreted an oral dose of 5 mg of the anti-depressant lortalamine (radiolabelled with carbon-14) mainly in the urine (98% during 5 days). Plasma 14C 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 of 14C then declined rapidly and were below the limits of detection (12 ng equiv./ml) at 24-36 h. Measurement of whole-blood 14C concentrations showed that there was some uptake into the blood cells (about 65% of the peak plasma 14C level). Radioactivity in the urine was mainly associated with unchanged drug and three metabolites. The major metabolite (about 50% urinary 14C) was identified by mass spectrometry as the N-demethylated compound and another metabolite as a keto derivative of lortalamine where oxidation had occurred in the piperidine ring.