High impact information on Desmethylsertraline

• Concentrations of sertraline and N-desmethylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples [1].
• Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant pairs [2].
• Sertraline and desmethylsertraline in human breast milk and nursing infants [3].
• CYP3A has been claimed to be involved in the biotransformation of sertraline to norsertraline [4].
• In the present study desmethylsertraline (DMS) was examined in two in vivo models of reuptake inhibition--elevation of extracellular 5-HT in the corpus striatum as measured by microdialysis and inhibition of firing of serotonin-containing dorsal raphe neurons [5].

Biological context of Desmethylsertraline

• Sertraline and desmethylsertraline pharmacokinetics were determined approximately weekly, and efficacy measures were assessed before drug administration and at the end of treatment [6].
• RESULTS: The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes [7].

Anatomical context of Desmethylsertraline

• However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers [7].

Associations of Desmethylsertraline with other chemical compounds

• Using HPLC, plasma levels of zolpidem, sertraline, and N-desmethylsertraline were determined at different times throughout the study and PK parameters derived [8].
• Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation [7].
• Fluoxetine, norfluoxetine, paroxetine, sertraline, desmethylsertraline, citalopram, desmethylcitalopram had little or no effect on CYP2C9 activity in vitro [9].

Gene context of Desmethylsertraline

• Sertraline is metabolized to desmethylsertraline, probably by CYP3A4 [10].
• METHODS: The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM) [7].

Analytical, diagnostic and therapeutic context of Desmethylsertraline

• Blood and urine samples were collected for 5 to 7 half-lives and sertraline, desmethylsertraline, fluoxetine, and norfluoxetine were determined by GC and HPLC techniques [11].

References