Investigating the Interaction between SSRI Drugs and Human Serum Albumin: Unraveling the Key Players in Antidepressant Delivery
Subject Areas : Journal of Chemical Health RisksVajagathali Mohammed 1 , Nikitha Shalom Richard 2
1 - Faculty of Allied Health Sciences, Chettinad Hospital and Research Institue, Chettinad Academy of Research and Education, Kelambakkam-603103, Tamilnadu, India
2 - Faculty of Allied Health Sciences, Chettinad Hospital and Research Institue, Chettinad Academy of Research and Education, Kelambakkam-603103, Tamilnadu, India
Keywords: Antidepressants, SSRI, Molecular docking, Depression, Human serum albumin,
Abstract :
Antidepressant drugs are medications used to treat various types of depressive disorders. They work by altering the balance of chemicals in the brain called neurotransmitters, which are involved in regulating mood. Selective Serotonin Reuptake Inhibitor (SSRI) is a class of antidepressant drugs that specifically target the neurotransmitter serotonin in the brain. They work by blocking the reuptake of serotonin, which increases the concentration of serotonin in the synaptic gap between neurons. HSA plays a crucial role as a transport protein, facilitating the delivery of hormones and various other ligands to their specific destinations within the body. The interaction of SSRI drugs with HSA and their binding mechanism in the HSA-SSRI system has not been extensively studied so far. The primary objective of this study is to investigate the binding affinity (BA) of SSRI drugs with HSA and identify the amino acids that bind to the antidepressant drug. The HSA protein structure (PDB ID: 1AO6) has been downloaded from the Protein Data Bank, and the SSRI antidepressant drugs structure were generated using ChemDraw. Our docking results showed that the SSRI drugs had a significant binding affinity (BA) (more negative than -5.0) with the HSA protein. Among them, the highest BA was found with vilazodone (-8.6), and the lowest BA was observed with escitalopram (-6.1). This suggests that SSRI drugs can bind to the HSA protein, potentially facilitating their transport through the bloodstream. HSA binding can also influence the drug's free concentration, which is the active form available for interaction with its target receptors in the brain.
1. Cloninger C.R., Zohar A.H., Cloninger K.M., 2010. Promotion of well-being in person-centered mental health care. Focus. 8(2), 165-179.
2. Bandelow B., Sher L., Bunevicius R., Hollander E., Kasper S., Zohar J., Möller H.J., Care W. T. F. o. M. D. i. P., WFSBP Task Force on Anxiety Disorders O., PTSD, 2012. Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care. International Journal of Psychiatry in Clinical Practice. 16(2), 77-84.
3. Fasipe O.J., 2019. The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents. IBRO Reports. 6, 95-110.
4. Pierz K.A., Thase M.E., 2014. A review of vilazodone, serotonin, and major depressive disorder. The primary care companion for CNS disorders. 16(1), 23088.
5. Urrila A., Paunio T., Palomäki E., Marttunen M., 2015. Sleep in adolescent depression: physiological perspectives. Acta Physiologica. 213(4), 758-777.
6. Wani T.A., Alsaif N., Alanazi M.M., Bakheit A.H., Zargar S., Bhat M.A., 2021. A potential anticancer dihydropyrimidine derivative and its protein binding mechanism by multispectroscopic, molecular docking and molecular dynamic simulation along with its in-silico toxicity and metabolic profile. European Journal of Pharmaceutical Sciences. 158, 105686.
7. Chamani J., Heshmati M., 2008. Mechanism for stabilization of the molten globule state of papain by sodium n-alkyl sulfates: spectroscopic and calorimetric approaches. Journal of Colloid and Interface Science. 322(1), 119-127.
8. Marouzi S., Rad A.S., Beigoli S., Baghaee P.T., Darban R.A., Chamani J., 2017. Study on effect of lomefloxacin on human holo-transferrin in the presence of essential and nonessential amino acids: Spectroscopic and molecular modeling approaches. International Journal of Biological Macromolecules. 97, 688-699.
9. Wani T.A., Bakheit A. H., Zargar S., Bhat M.A., Al-Majed A. A., 2019. Molecular docking and experimental investigation of new indole derivative cyclooxygenase inhibitor to probe its binding mechanism with bovine serum albumin. Bioorganic Chemistry. 89, 103010.
10. Kou S.-B., Lin Z.-Y., Wang B.-L., Shi J.-H., Liu Y.-X., 2021. Evaluation of the binding behavior of olmutinib (HM61713) with model transport protein: Insights from spectroscopic and molecular docking studies. Journal of Molecular Structure, 1224, 129024.
11. Rabbani G., Lee E. J., Ahmad K., Baig M. H., Choi I., 2018. Binding of tolperisone hydrochloride with human serum albumin: effects on the conformation, thermodynamics, and activity of HSA. Molecular pharmaceutics, 15 (4), 1445-1456.
12. Alam M. M., Abul Qais F., Ahmad I., Alam P., Hasan Khan R., Naseem I., 2018. Multi-spectroscopic and molecular modelling approach to investigate the interaction of riboflavin with human serum albumin. Journal of Biomolecular Structure and Dynamics, 36 (3), 795-809.
13. BK I., 2022. Pharmacokinetics of Clozapine: An Investigate the Potential Molecular Mechanisms of Action. Journal of Chemical Health Risks, 12 (2), 247-254.
14. Wilcox C. S., 2002. New insights into diuretic use in patients with chronic renal disease. Journal of the American Society of Nephrology, 13 (3), 798-805.
15. Detke M. J., Lucki I., 1995. Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth. Behavioural brain research, 73 (1-2), 43-46.
16. Bohnert T., Gan L.-S., 2013. Plasma protein binding: from discovery to development. Journal of pharmaceutical sciences, 102 (9), 2953-2994.
17. McElnay J., D’arcy P., 1983. Protein binding displacement interactions and their clinical importance. Drugs, 25, 495-513.
18. Khammari A., Saboury A. A., Karimi-Jafari M. H., Khoobi M., Ghasemi A., Yousefinejad S., Abou-Zied O. K., 2017. Insights into the molecular interaction between two polyoxygenated cinnamoylcoumarin derivatives and human serum albumin. Physical Chemistry Chemical Physics, 19 (15), 10099-10115.
19. Schwartz T. L., Siddiqui U. A., Stahl S. M., 2011. Vilazodone: a brief pharmacological and clinical review of the novel serotonin partial agonist and reuptake inhibitor. Therapeutic advances in psychopharmacology, 1 (3), 81-87.
20. Owens M. J., Knight D. L., Nemeroff C. B., 2001. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biological psychiatry, 50 (5), 345-350.
21. Shao X., Ai N., Xu D., Fan X., 2016. Exploring the interaction between Salvia miltiorrhiza and human serum albumin: Insights from herb–drug interaction reports, computational analysis and experimental studies. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 161, 1-7.
22. Coelho M. M., Fernandes C., Remião F., Tiritan M. E., 2021. Enantioselectivity in drug pharmacokinetics and toxicity: Pharmacological relevance and analytical methods. Molecules, 26 (11), 3113.