Ratan Singh, Sabita Pokhre, Preeti Gautam and Amar Jyoti das
Accepted Abstracts: Pharmaceut Reg Affairs
The side effects of contraceptives in general and combined oral contraceptives (COC) in particular are numerous and are limiting factors in many cases leading to cease their use. At the same time the combined oral contraceptives or synthetic estrogens are increasingly being used in Medicine today. Weight gain, migraine and depression are some of the side effects of COC and also three of them are associated with disorder in serotonin level. Here we hypothesized that EthinylEstradiol (EE) may affect serotonin function by binding to serotonin receptors as off-target ones (realizing that serotonin receptors and estrogen receptors coexist in a wide varieties of tissues); hence explaining the mechanism by which the aforementioned side effects take place. Having known that the receptors` tertiary structures are not solved yet, the only choice was to construct the 3D of receptors based on previously solved ones using comparative modeling techniques. the homology models for serotonin receptors (5ht2a and 5ht2c) were generated using I-TASSER web server and MOE program (Molecular operating environment), and then the structures were compared using Dalilite web server against a high resolution beta2 adrenergic receptor 2RH1, accordingly the best one was that predicted by I-TASSER web server. The binding sites predicted by I-TASSER for both receptors, were highly consistent with those predicted by others. Molecular docking of the ligands was performed using PatchDock web server and SYBYL-X program. The final results strongly support our hypothesis furthermore it highlights the issue of target specificity and how important is it when synthesizing any drug.
Rehab Yousif finished her MSC in Molecular medicine July 2012 with distinction degree from Institute of Endemic Diseases (IEND), University of Khartoum. She is a teaching assistant in the department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Khartoum.