Abstract
The tricyclic antidepressant (TCA) tertiary amines imipramine (IMI) and amitriptyline (AMI) were found, soon after their introduction as drugs, to have active demethyl metabolites—desipramine (DMI) and nortriptyline (NT) (figure 1). These two secondary amines were later introduced as antidepressant drugs. Similarly the potent serotonin (5-HT) uptake inhibitor chlorimipramine (CI) is demethylated to an active secondary amine. In almost every patient the steady state plasma levels of demethylchlorimi-pramine (DMCI) exceeded those of the parent drug (Träskman et al., 1979; Thorén et al., 1980). As the demethyl metabolite is a potent inhibitor of norepinephrine (NE) uptake, demethylation changes the pharmacodynamic profile of the drug (Träskman et al., 1979; Thorén et al., 1980).
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Bertilsson, L. et al. (1981). Active metabolites of antidepressants: novel aspects of hydroxylation and demethylation in man. In: Usdin, E., Dahl, S.G., Gram, L.F., Lingjærde, O. (eds) Clinical Pharmacology in Psychiatry. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-05929-4_13
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DOI: https://doi.org/10.1007/978-1-349-05929-4_13
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