TRYPTAMINE - A POSSIBLE ENDOGENOUS SUBSTRATE FOR CYP2D6

The fact that CYP2D6 is not only expressed in liver but also in brain and the clinical association of this cytochrome with Parkinson's disea se suggests the possibility of existence of some endogenous substrate, and among these perhaps one or more neurotransmitters could be metabo lized by CYP2D6. In this study we explored such a possibility by study ing the modulation of CYP2D6 activity by several neurotransmitters. Ou r findings confirm the occurrence of a competitive inhibition of dextr omethorphan O-demethylation in the presence of tryptamine, with a K-i value of 44.6 mu M. Such activity is NADPH dependent and is inhibited by quinidine and CYP2D6-specific substrates. The product of the reacti on is tryptophol. These results suggest that tryptamine may be an endo genous substrate of CYP2D6.