Molecular Docking studies of Benzodiazepine Derivatives With GABA(B) Receptor

Year : 2024 | Volume :01 | Issue : 02 | Page : 1-14
By

Satish Kumar Sarankar

Sushma Somkuwar

  1. Professor& Principal,Faculty of Pharmacy, Mansarovar Global University, Sehore, Madhya Pradesh, India
  2. Associate Professor, School of Pharmacy, LNCT University, Bhopal, Madhya Pradesh, India

Abstract

Benzodiazepines (BZDs) are pharmacologically significant compounds that act by binding to GABA A neurotransmitter receptors, subsequently augmenting GABA-induced chloride ion flux, consequently inducing neuronal hyperpolarization. Benzodiazepines are commonly used in the treatment of sleep disorders, anxiety, muscle spasms, seizure disorders, and some forms of depression. The primary inhibitory neurotransmitter, GABA, functions on two types of receptors: the ligand-gated GABA A/C receptors and the G protein-coupled GABA B receptors. These neurotransmitters play crucial roles in modulating numerous synapses, influencing both pre- and post-synaptic activity, and remain noteworthy targets for the treatment of various brain disorders, including addiction.Since both the GABA A and GABA B are subunits of the same receptor, binding affinity of BZDs to GABA B receptor have been assessed using docking approach in present work. Some of the most commonly used BZDs were preferred for docking and studies showed that they have got the affinity to bind with GABA B receptor too. This study opens a new path for repurposing BZDs for variety of pharmacological actions as well as for researchers to work in this new direction.

Keywords: Benzodiazepines, GABA A & B, Docking, Anxiety

[This article belongs to International Journal of Toxins and Toxics(ijtt)]

How to cite this article: Satish Kumar Sarankar, Sushma Somkuwar. Molecular Docking studies of Benzodiazepine Derivatives With GABA(B) Receptor. International Journal of Toxins and Toxics. 2024; 01(02):1-14.
How to cite this URL: Satish Kumar Sarankar, Sushma Somkuwar. Molecular Docking studies of Benzodiazepine Derivatives With GABA(B) Receptor. International Journal of Toxins and Toxics. 2024; 01(02):1-14. Available from: https://journals.stmjournals.com/ijtt/article=2024/view=134049

Browse Figures

References

  1. Chebib M, Johnston GA, The ‘ABC’ of GABA receptors: A brief review. Clin Exp Pharmacol Physiol. 1999; 26(11):937-40
  2. Rudolph U, Mohler H, GABA-based therapeutic approaches: GABAA receptor subtype functions. Curr OpinPharmacol. 2006; 6:18-23
  3. Fritschy JM, Panzanelli P, GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system. Eur J Neurosci. 2014; 39:1845-1865
  4. Cryan JF, Kaupmann K, Don’t worry ‘B’ happy!: A role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci. 2005; 26:36-43
  5. Jacobson LH, Cryan JF, Evaluation of the anxiolytic-like profile of the GABAB receptor positive modulator CGP7930 in rodents. Neuropharmacology. 2008; 54:854-862
  6. Bettler B, Kaupmann K, Mosbacher J, Gassmann M, Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev. 2004; 84:835-867
  7. Gaiarsa JL, Porcher C, Emerging neurotrophic role of GABAB receptors in neuronal circuit development. Front Cell Neurosci. 2013; 7:206
  8. Schwartz-Bloom RD, Sah R, Gamma-Aminobutyric acid (A) neurotransmission and cerebral ischemia. J Neurochem. 2001; 77:353-371
  9. Wu C, Sun D, GABA receptors in brain development, function, and injury. Metab Brain Dis. 2015; 30:367-379
  10. Terunuma M, Diversity of structure and function of GABAB receptors: A complexity of GABAB-mediated signaling. Proc JpnAcad Ser B Phys Biol Sci. 2018; 94:390-411
  11. Rudolph U, Mohler H, GABAA receptor subtypes: Therapeutic potential in Down syndrome, affective disorders, schizophrenia, and autism. Annu Rev PharmacolToxicol. 2014; 54:483-507
  12. Wu Y, Wang W, Richerson GB, Vigabatrin induces tonic inhibition via GABA transporter reversal without increasing vesicular GABA release. J Neurophysiol. 2003; 89:2021-2034
  13. Heaney CF, Kinney JW, Role of GABA(B) receptors in learning and memory and neurological disorders. NeurosciBiobehav Rev. 2016; 63:1-28
  14. Hulse G, Kelty E, Hood S, Norman A, Basso MR, Reece AS, Novel Indications for Benzodiazepine Antagonist Flumazenil in GABA Mediated Pathological Conditions of the Central Nervous System. Curr Pharm Des. 2015; 21(23):3325-42
  15. Berezhnoy D, Gibbs TT, Farb DH, Docking of 1,4-benzodiazepines in the α1/γ2 GABAA receptor modulator site. Mol Pharmacol 2009; 76:440-450,
  16. Middendorp S J, Puthenkalam R, Baur R, Ernst M, Sigel E, Accelerated discovery of novel benzodiazepine ligands by experiment-guided virtual screening. ACS Chem Biol 2014; 9:1854-1859
  17. Sieghart W, Allosteric Modulation of GABAA Receptors via Multiple Drug-Binding Sites Adv Pharmacol 2015; 72:53-96
  18. Whissell PD, Rosenzweig S, Lecker I, Wang DS, Wojtowicz JM, Orser BA, γ-aminobutyric acid type A receptors that contain the δ subunit promote memory and neurogenesis in the dentate gyrus. Ann. Neurol. 2013; 74:611-621
  19. Galeffi F, Sinnar S, Schwartz-Bloom RD, Diazepam promotes ATP recovery and prevents cytochrome c release in hippocampal slices after in vitro ischemia. J Neurochem. 2000; 75:1242-1249
  20. Schwartz RD, Huff RA, Yu X, Carter ML, Bishop M, Post-ischemic diazepam is neuroprotective in the gerbil hippocampus. Brain Res. 1994; 647:153-160
  21. Centonze D, Saulle E, Pisani A, Bernardi G, Calabresi P, Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia. Brain. 2001; 124:1855-1865
  22. Schwartz-Bloom RD, Miller KA, Evenson DA, Crain BJ, Nadler JV, Benzodiazepines protect hippocampal neurons from degeneration after transient cerebral ischemia: an ultrastructural study. Neuroscience. 2000; 98:471-484

Regular Issue Subscription Original Research
Volume 01
Issue 02
Received February 12, 2024
Accepted February 21, 2024
Published March 2, 2024