Insights into the interaction mechanism between tiagabine hydrochloride and two serum albumins

Abstract

Tiagabine could bind in Sudlow site II of HSA and BSA.

Human Serum Albumin-Occupying-Based Fluorescence Turn-On Analysis of Antiepileptic Drug Tiagabine Hydrochloride

“…Tiagabine hydrochloride (TGB) is a commonly used drug in the clinical treatment of convulsion and epilepsia via pharmacological regulating γ-aminobutyric acid in neurons/glial cells or at the synaptic site. − The therapeutic concentration for TGB is no more than 40 ng/mL for nearly 80% of the patients . Over administration of TGB to patients is proved to cause a series of side effects, including depression, abdominal pain, abnormal cognitive ability, decreased mental retardation. − Worse, the abuse of TGB is also found to have high risk in generating suicidal thoughts or behaviors . Therefore, development of accessible and point-of-care assay for detection of TGB has become an imminent task for instructing its safe use in clinical practice.…”

“…Up to now, only high performance liquid chromatography (HPLC)-based methods was exploited to analyze TGB, which suffers from drawbacks of being technically demanding, lack of sensitivity, and costly/time-consuming. , Fluorescence sensors have gained considerable attention in recent years for pharmaceutical analysis due to their operability, high sensitivity, and fast-speed. − In the pharmacokinetic studies, TGB has been discovered to bind with human serum albumin (HSA) through entering the hydrophobic cavity in Sudlow site II of HSA and forming specific cation-π bonds with the surrounding amino acids residues . Meanwhile, some HSA-based organic fluorescent probes, such as solvatochromic dyes, − twisted intramolecular charge transfer fluorophores, , and disassembly/aggregation induced emission based fluorophores, − were discovered displaying a fluorescence enhancement upon occupying the hydrophobic binding sites on of HSA.…”

“…5−9 Worse, the abuse of TGB is also found to have high risk in generating suicidal thoughts or behaviors. 10 Therefore, development of accessible and point-of-care assay for detection of TGB has become an imminent task for instructing its safe use in clinical practice. The determination of the drug in urine is a common clinical method for studying pharmacokinetics.…”

“…13−16 In the pharmacokinetic studies, TGB has been discovered to bind with human serum albumin (HSA) through entering the hydrophobic cavity in Sudlow site II of HSA and forming specific cation-π bonds with the surrounding amino acids residues. 10 Meanwhile, some HSAbased organic fluorescent probes, such as solvatochromic dyes, 17−19 twisted intramolecular charge transfer fluorophores, 20,21 and disassembly/aggregation induced emission based fluorophores, 22−26 were discovered displaying a fluorescence enhancement upon occupying the hydrophobic binding sites on of HSA. Inspired from site-specific occupying of HSA, some of fluorescent dyes have been facilely applied for probing binding sites of individual drug-based drug displacement reactions.…”

“…In a typical assay, 5 μM PTAI solution and 40 μM HSA solution were mixed first for measuring the initial fluorescence. Subsequently, a series of concentration gradients of DNSA or ibuprofen (10,20,50, 70, 100 μM) were added to the mixed solution to measure the fluorescence spectrum.…”