Nor₂Chlorpromazine Sulphoxide and 3,4-Dimethoxyphenethylamine

Abstract

SEVERAL workers have found a spot isographic with 3,4-dimethoxyphenethylamine (DMPEA) in urine chromatograms of some schizophrenic patients but never or rarely in those of non-schizophrenic persons^1–3. A metabolite of chlorpromazine (CPZ), however, noted⁴ to have been identified as nor₂chlorpromazine Sulphoxide (N₂CPSO)⁵, causes a spot close to or isographic with DMPEA in the chromatographic system originally used to detect the spots apparently diagnostic of schizophrenia^4,5 (referred to below as system 1). If a phenothiazine metabolite caused the apparently diagnostic spots (the pink spots) the following conditions must be fulfilled. (1) The R_F for the metabolite in system 1 should be almost identical to that of DMPEA because fifteen pink spots were originally studied and even a small consistent difference in R_F between these spots and authentic DMPEA would have been detectable. (2) The metabolite must be isographic with DMPEA in the two-way system used by Kuehl et al.², for they reported that certain samples found positive by Friedhoff and van Winkle showed a ninhydrin positive spot isographic with DMPEA in their system. (3) The metabolite must persist in urine after the parent drug has been stopped because all of the original patients and many of those found subsequently to have pink spots had been withdrawn from drugs for at least 2 weeks. (4) The metabolite must give a pink spot with modified Ehrlich's reagent (DABA) following ninhydrin-pyridine and a negative reaction with DABA alone because this test was applied to the original spots¹. Also, an explanation must be found for the fact that material isolated from the original spots was indistinguishable from authentic DMPEA in several sensitive tests of identity^1,11 and for the fact that Takesada et al., who were aware of the problem of confounding drug metabolites and particularly N₂CPSO, found pink spots in the urine of schizophrenic patients and others as well⁵.