An Innovatory GABA Receptor Modulator and Liver Oxidase System Microsomal Cytochrome P450 Activator in Patients with Alcoholism
PHARMACEUTICAL CHEMISTRY JOURNAL(2021)
摘要
Molecular docking studies (in Schrödinger and Glide software) showed that the molecule m-Cl-BHU ( meta -chlorobenzhydrylurea) is complementary to the benzodiazepine binding site of GABA A 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 [ 3 H]flunitrazepam with the benzodiazepine site of brain GABA A 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 ( T 1/2 , Cl t , 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.
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关键词
anticonvulsant, γ, -aminobutyric acid, meta-chlorobenzhydrylurea, molecular docking, receptor, pharmacokinetics, ethanol
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