METABOLISM OF BW-1370U87 BY CRUDE LIVER HOMOGENATES FROM SEVERAL SPECIES - AN INVITRO METHOD FOR PRELIMINARY INVESTIGATION OF SPECIES-DIFFERENCES IN METABOLISM

We employed broken cell liver preparations in order to investigate pot ential species-specific differences in the metabolism of BW 1370U87, a new selective and reversible MAO-A inhibitor. The drug metabolizing c apacity of crude liver homogenates from rat, dog, cat, monkey, and man was assessed based on the utilization of BW 1370U87 and the appearanc e of suspected metabolites. When incubated with liver homogenates (37- degrees-C) in the presence of a cofactor preparation designed to gener ate TPNH, BW 1370U87 (1 or 10-mu-M) was metabolized in a species and t ime dependent manner. The rate of disappearance of BW 1370U87 was more rapid in dog and cat preparations than those of rat, monkey and man. The appearance of metabolites coincided with the disappearance of BW 1 370U87. Three metabolites, identified and synthesized as BW 183U88, BW 380U88, and BW 330U88 appeared in all five species. These metabolites were also found to be selective MAO-A inhibitors both in vitro and ex vivo and may contribute to the overall activity exhibited by the pare nt molecule.