Metabolism of BW 1370U87 by crude liver homogenates from several species: An in vitro method for preliminary investigation of species differences in metabolism
✍ Scribed by Mr. Ronald M. Norton; Helen L. White; Barrett R. Cooper
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 304 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0272-4391
No coin nor oath required. For personal study only.
✦ Synopsis
We employed broken cell liver preparations in order to investigate potential species-specific differences in the metabolism of BW 13701187, a new selective and reversible MAO-A inhibitor. The drug metabolizing capacity of crude liver homogenates from rat, dog, cat, monkey, and man was assessed based on the utilization of BW 1370U87 and the appearance of suspected metabolites. When incubated with liver homogenates (37°C) in the presence of a cofactor preparation designed to generate TPNH, BW 13701187 (1 or 10 pM) was metabolized in a species and time dependent manner. The rate of disappearance of BW 13701187 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 13701187. Three metabolites, identified and synthesized as BW 183U88, BW 380U88, and BW 3301188 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 parent molecule.