Abstract
The present state of our knowledge concerning the metabolism of CPZ in humans is as follows:
Non-polar metabolites — All eight of the postulated metabolites have been reported, with nor-CPZ-SO and bis-nor-CPZ-SO being present in the largest amounts and CPZ and CPZ-SO in lesser amounts.
Moderately polar metabolites — Only CPZ-NO is present in substantial amounts. We have detected two acidic, but non-basic, metabolites by TLC and tentatively identified them as N-β-carboxyethyl derivatives. The concentration of free phenols seems to be very low in fresh urine.
Highly polar metabolites — We have seen at least 15 glucosiduronides and/or sulfates by TLC.
The isolation of representative reference compounds from the highly polar fraction and the determination of their chemical structures will permit the development of analytical techniques for their routine estimation. This information may disclose differences in the metabolic patterns of different patients and may permit the correlating of drug responsiveness with specific metabolic processes.
Obviously, the finding of any anomalous metabolism could have many consequences: it might provide a means of understanding why some patients are drug-responders while others are drug-refractory. Also, vitamins, coenzymes, or other substances which are known to have a role in that particular type of metabolic reaction could be used in an attempt to modify the action of the currently used phenothiazines. Finally, if a certain metabolic pathway is found to lead to either especially high or especially low therapeutic efficacy, medicinal chemists could ‘tailor-make’ a molecule which either facilitates or blocks that particular metabolic sequence in order to improve the clinical usefulness of the phenothiazine ‘tranquillizers’.