Study on the binding of chiral drug duloxetine hydrochloride to human serum albumin

Duloxetine holds a special promise as an antidepressant, and its effect depends on its binding to human serum albumin (HSA). For this reason, the binding mechanism of duloxetine with HSA was investigated. The specific binding site in HSA was identified and binding constants were determined. Duloxetine could compete with dansyl-L-proline (DLP), a site II marker for binding to site II. Binding constants between duloxetine and HSA were 1.75 × 103 L mol−1 and 3.74 × 103 L mol−1 at pH 7.4 and pH 8.5, respectively. The interaction process of enantiomers and HSA was susceptible to pH change. It was concluded that specific binding position of duloxetine was located in site II, and the B conformation of HSA possibly excelled the N conformation in identifying and binding to enantiomers.

Duloxetine can quench DLP–HSA complex fluorescence (pH = 7.4 (solid); pH = 8.5 (dashed line); duloxetine (○); R-isomer (■)), and this meant the specific binding site of duloxetine was located in site II of HSA.Figure optionsDownload as PowerPoint slide