Molecular spectroscopic studies examining the interactions between phenobarbital and human serum albumin in alcohol consumption

Background: Alcohol dependence is associated with a wide range of serious mental, physical, and social consequences and is one of the most common chronic diseases worldwide. Barbiturates, which are a first-line treatment in the clinic for alcohol withdrawal, may result in combined barbiturate and alcohol use. Their co-use abuse may promote synergistic effects between barbiturates and alcohol in vivo. Objective: To investigate the effects of different alcohol concentrations on the synergistic effects of phenobarbital and alcohol. Methods: The interactions between phenobarbital and human serum albumin (HSA) and the effects of different alcohol concentrations on the binding behaviors of the phenobarbital-HSA system were investigated by molecular docking and spectroscopic methods, including fluorescence spectroscopy and UV-visible absorption spectroscopy. Results: Experimental results revealed that phenobarbital can be stored and carried by HSA. The presence of alcohol (≤1.96 × 10–2 M) can increase the proportion of free phenobarbital and shorten the half-life and storage time of phenobarbital in the blood, thereby enhancing its bioactive efficacy. The binding constants (Kb) of the phenobarbital-HSA system decrease in the presence of alcohol (≥2.61 × 10–2 M), which suggests that phenobarbital should be quickly cleared from blood, thereby decreasing the activity of phenobarbital. Conclusions: The effects of alcohol on the transposition of phenobarbital by HSA at the beginning of the barbiturate metabolic process play an important role in the synergistic effects of phenobarbital and alcohol. This mechanism may be significant for the clinical dosage of patients with alcohol dependence.