Nomifensin metabolites

While Funk et al. did not use temperatures above 30 °C during the irradiation times discussed above, Sistovaris combined UV irradiation with simultaneous heating (70 °C, 2 h) of the TLC layers [24]. After this treatment nomifensine and its metabolites appeared as intense yellow fluorescent ehromatogram zones on a dark background. 

Nomifensine and metabolites 70°C, 2 h + UV2S4 Heating and simultaneous UV irradiation produced intense yellow fluorescence (Xn > 460 nm, cut off filter). [30]... 

In contrast to a-methyldopa-induced hemolytic anemia, most drug-induced hemolytic anemia, especially for penicillins [34] and cephalosporins [35], involves drug-dependent antibodies, presumably because the drug acts as a hapten to directly modify erythrocytes or form immune complexes [36], However, there are many examples where a drug, such as nomifensine, induces both drug- (or metabolite)-dependent and drug-... 

Lastly, nomifensine was an interesting antidepressant that also had noradrenaline, dopamine and, due to its 4-hydroxy metabolite, serotonin reuptake properties. It was withdrawn some years ago because of the occurrence of haemolytic anaemia in a small number of patients. It was a particularly effective drug in the treatment of depression in patients with epilepsy as, unlike many antidepressants available at that time, it did not affect the seizure threshold. 

With its 2-carbon bridge across the middle, maprotiline (Fig. 12-26) is technically a tetracyclic compound, yet it behaves as a secondary amine TCA (i.e., a relatively selective NE reuptake). The drug s second-generation standing is purely chronological. It has been in the U.S. market since 1981. Amoxapine, which was marketed the same year, is, of course, the N4-demethylated antipsychotic loxapine (Fig. 12-26). It has been suggested the cumulation of the 8-OH metabolite may be responsible for the inhibition of NE uptake and account for the antidepressant effect. Nomifensine, which is a tetrahydroisoquinoline with potential as an inhibitor of NE and DA, but not 5-HT, was withdrawn in 1987 for toxicity reasons. 

Salama A, Mueller-Eckhardt C (1985) The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia. N Engl J Med 313 469 74 Salama A, Mueller-Eckhardt C (1987) On the mechanisms of sensitization and attachment of antibodies to RBC in drag-induced immune hemolytic anemia. Blood 69 1006-1010 Salama A, Gottsche B, Mueller-Eckhardt C (1991) Autoantibodies and drag- or metabolite-dependent antibodies in patients with diclofenac-induced immune haemolysis. Br J Haematol 77 546-549... 

Obach, S.R. and Dalvie, D.K. (2006) Metabolism of nomifensine to a dihydroisoquinolinium ion metabolite by human myleoperoxidase, hemoglobin, monamine oxidase A, and cytochrome P450 enzymes. Drug Metabolism and Disposition, 34, 1310-1316. 

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