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

T. V. Shushpanova, N. A. Bokhan, K. S. Stankevich, T. P. Novozheeva, A. I. Mandel’, E. D. Schastnyi, N. I. Kisel’, O. V. Shushpanova, V. V. Udut, S. M. Safronov, R. S. Boev, E. M. Knyazeva

Research output: Contribution to journalArticlepeer-review

Abstract

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 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.

Original languageEnglish
Pages (from-to)1093-1100
Number of pages8
JournalPharmaceutical Chemistry Journal
Volume54
Issue number11
DOIs
Publication statusPublished - Feb 2021

Keywords

  • anticonvulsant
  • ethanol
  • meta-chlorobenzhydrylurea
  • molecular docking
  • pharmacokinetics
  • receptor
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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