In silico toxicity investigation of Methaqualone’s conjunctival, retinal, and gastrointestinal hemorrhage by molecular modelling approach

Abstract

ABSTRACT Methaqualone was once used to treat insomnia as a hypnotic agent. Methaqualone, like other sedative–hypnotics, is a central nervous system depressant that increases gamma-aminobutyric acid (GABA) activity. Methaqualone toxicity data showed that it inhibits platelet aggregation, increases prothrombin time and partial thromboplastin time, and lowers factors V and VII, all of which can cause retinal, conjunctival, and gastrointestinal hemorrhage. In silico investigation showed that Methaqualone antagonises Vitamin K in the extrinsic and intrinsic pathways of blood clotting, which leads to an increase in prothrombin time and partial thromboplastin time and lowers factors V and VII. Further, a molecular modelling study proved that inhibition of the P2Y12R by Methaqualone is responsible for the inhibition of platelet aggregation. This study systematically correlates all Methaqualone's blood-related toxicity, which results in conjunctival, retinal, and gastrointestinal hemorrhage.