Abstract
Imipramine is a renowned tricyclic anti-depressant molecule. It is known to be highly potent and efficient as compared to any other antidepressants available. There are numerous literature reports which elucidate the metabolic pathways of Imipramine. There are also various reports showing the effect of substrate and time on metabolism of Imipramine. Most of analytical methods used in these studies were of HPLC and /or of LC-MS. These studies have also been extended to identification of specific isoforms of cytochrome P450 family responsible for the metabolism of Imipramine as is outlined. Further, LC-MS based studies have also been reported on the metabolism of Imipramine in in-vitro systems including human liver microsomes and its extrapolation on human oral bioavailability data. However, till date, there has been no published report on the systematic metabolic stability of this molecule in pooled mouse and dog liver microsomes. The present study was undertaken with the aim to understand the metabolic stability of imipramine in liver microsomes of different species including human, wistar rat, CD1 mouse and male beagle dog. We have also attempted to outline the differences between the metabolic stability in these four species. The reaction samples were scanned for specific m/z values corresponding to reported metabolites, which in turn confirms microsomal metabolism.
Highlights
Imipramine, a prototype of the tricyclic antidepressant class, is one of the most effective molecules available for the treatment of depression
Metabolism studies were initially started in human liver microsomes, which were extended to rat liver microsomes [4] and mouse liver microsomes [5]
Till date almost all metabolic pathways of imipramine have been established with proper framework of data
Summary
Imipramine, a prototype of the tricyclic antidepressant class, is one of the most effective molecules available for the treatment of depression. Because of its unsurpassed effects, it is considered as “Gold standard” for assessing novel antidepressant molecules. In case of in-vivo and in-vitro studies, researchers have mainly contributed on outlining metabolism of imipramine. Various phase I and phase II metabolites have been reported [2]. Among the phase I metabolites, the major metabolites are desipramine, 2-hydroxy imipramine, 10-hydroxy imipramine, N-oxide derivative of imipramine. The phase II metabolites mainly include glucuronide conjugates [3]. Numerous reports have elucidated the structures of major metabolites and simultaneously rate of formation of those metabolites in different species [6]
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