The effects of CQ and QN observed in the present studies were most striking for CYP2D6 inhibition, with very modest effects on the oxidative deamination products of MAO. In hepatocytes, the inhibitory effects were most striking on the CYP2D6 related products. The presence of CQ and QN did not appear to significantly inhibit the MAO-dependent pathway in hepatocytes. The inhibitory effects on CYP2D6 appeared to enhance the MAO-mediated metabolism as demonstrated in a mild increase in formation of CPQ, and the metabolites corresponding to m/z 241. A surprising inhibition was observed, however, on the formation of the glucuronides of CPQ and PQ alcohol in the human hepatocytes. This would be expected to facilitate the accumulation of the primary oxidative deamination metabolites. This finding is consistent with the report that CQ increased circulating CPQ concentrations when co-administered with PQ in humans . The implications of this are not known, but such metabolites could theoretically exert more pronounced pharmacodynamic effects and may contribute to the observed alteration in PQ response in the presence of CQ and QN.