An Innovatory GABA Receptor Modulator and Liver Oxidase System Microsomal Cytochrome P450 Activator in Patients with Alcoholism

Molecular docking studies (in Schrodinger and Glide software) showed that the molecule m-Cl-BHU (meta-chlorobenzhydrylurea) is complementary to the benzodiazepine binding site of GABAA receptors. Binding energy was low (-11.14 kcal/mol); m-Cl-BHU interacts with the key amino acids at the α1γ2 interface: Tyr159, Tyr209, and H101 Phe77 with high fit to the dG insertion model: 0.741. Binding of [3H]flunitrazepam with the benzodiazepine site of brain GABAA receptors increased in rats with experimental alcoholism treated with m-Cl-BHU at a dose of 100 mg/kg for 14 days. Changes in pharmacokinetic parameters (T1/2, Clt, MRT, MET, and AUC) of the model substrate antipyrine in saliva were seen in healthy volunteers and male patients with alcoholism using Galodif (m-Cl-BHU) at a dose of 300 mg/day for 21 days. Elimination of antipyrine in patients with alcoholism was increased due to activation of microsomal cytochrome P450 in the liver oxidase system.