Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes

Abstract The present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I II enzymes in rat liver microsomes (RLM) as an alternative separate testing with recombinant enzymes. This approach allows for more time-saving cost-effective screening newly discovered drugs. We also considered that lack results II, including UGT, often creates problems correct selection valuable compounds. Moreover, data set is richer contest provides medical scientist determine susceptibility drugs undergo then II. In work, we have shown IS-noh was metabolized vitro oxidation product, which next transformed UGTs glucuronide. showed previously known product changed no reported glucuronidation UDP-glucuronosyltransferases. addition, unlike IS-noh, did not prove be substrate UGTs. Therefore, tricyclic antidepressants depending on structure can trigger a different response after contact UGT Some will metabolize directly UGTs, others only activation