Theoretical Investigation of Physicochemical Properties, Bioactivity, and Toxicity of Common Anxiety Medications

Abstract Physicochemical properties, bioactivity scores, toxicity, chemical reactivity descriptor (GCRD), polarizability, and UV–vis spectroscopy of 10 common medicines used for the treatment of anxiety have been investigated to understand their activity and adverse effect in the human body. GCRD, polarizability, and UV–vis data of the drug molecules have been analyzed at the density functional M06‐2X/cc‐pVTZ level. Molinspiration, Osiris Property Explorer, and the SwissTargetPrediction tools have been used to study the molecular and physicochemical properties, drug likeness/bioactivity scores, and toxicity of the drug molecules. The calculated results show that all drug molecules have good bioavailability and are orally active, which corroborate with the clinical data. Most of the theoretical results are first reported, and the predicted results agree well with the clinical data and published reports wherever available. The calculated GCRD parameters confirm that chlordiazepoxide ( D3 ) is the most reactive drug molecule. Drug likeness and drug score indicate that alprazolam ( D1 ), chlordiazepoxide ( D3 ), paroxetine ( D7 ), and selegiline ( D9 ) are safe medicines for humans. The predicted toxicities also substantiate the clinical data. The BOILED‐Egg plot illustrates that as alprazolam ( D1 ) and paroxetine ( D7 ) are the substrates of the P‐glycoprotein (PGP+), they are actively pumped up from the brain or to the gastrointestinal lumen.