We suggested that this feature might give clozapine a higher therapeutic effect.
📌 3 Maddede Bu Makale
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Amaç & Hipotez:In order to find some clues as to why clozapine is a more effective drug than the sertindole and quetiapine, we investigated the molecular structures of these three molecules and calculated their structural properties by Density Functional Theory (DFT) technique.
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Temel Bulgular & Veri:To test this hypothesis, we measured the binding of three drugs to D1 and D2 dopamine receptors by molecular docking.
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Sonuç & Katkı:We suggested that this feature might give clozapine a higher therapeutic effect.
In order to find some clues as to why clozapine is a more effective drug than the sertindole and quetiapine, we investigated the molecular structures of these three molecules and calculated their structural properties by Density Functional Theory (DFT) technique. In this article, we suggested that clozapine has different binding possibilities depending on the dopamine level in the medium. If so, it can be understood why clozapine is more effective in resolving clinical problems caused by different dopamine levels in the frontal and subcortical regions. To test this hypothesis, we measured the binding of three drugs to D1 and D2 dopamine receptors by molecular docking. We found that clozapine had a greater potential for binding with D1 and D2 receptors. We suggested that this feature might give clozapine a higher therapeutic effect.
ÜNAL, S., KARAKAPLAN, M., ÖZ, E., YILMAZ, İ., ALTIN, S., BAYRİ, A. (2019). WHY IS CLOZAPINE MORE EFFECTIVE THAN OTHER ATYPICAL ANTIPSYCHOTICS? DENSITY FUNCTIONAL THEORY AND MOLECULAR DOCKING APPROACH. Bartın Üniversitesi Uluslararası Fen Bilimleri Dergisi, Cilt: 2 - Sayı: 2, 207–215. https://ajindex.com/articles/740547
Aranda R., Villalba K., Ravina E., Masaguer C.F., Brea J., Areias F., Dominguez E., Selent J., Lopez L., Sanz F., Pastor M. & Loza M.I. (2008). Synthesis, Binding Affinity, and Molecular Docking Analysis of New Benzofuranone Derivatives as Potential Antipsychotics. J. Med. Chem., 51(19), 6085-6094
Arnt J., Hyttel J. & Sánchez C. (1992). Partial and full dopamine D1 receptor agonists in mice and rats: relation between behavioural effects and stimulation of adenylate cyclase activity in vitro. European Journal of Pharmacology, 213(2), 259–267
Bayri A., Unal S., Altin S., Bulut F. & Dayanc B. E. (2016). Altered isotope charge distribution of acetylcholine neurotransmitter and Myasthenia Gravis. Medical Hypotheses, 89, 84–88
Becke A. D. (1993). A new mixing of Hartree–Fock and local density‐functional theories. The Journal of Chemical Physics, 98(2), 1372–1377. 5. de Keyser J., De Backer J.-P., Vauquelin G. & Ebinger G. (1990). The effect of aging on the D1 dopamine receptors in human frontal cortex. Brain Research, 528(2), 308–310
Devoto P., Flore G., Vacca G., Pira L., Arca A., Casu M. A., Pani L. & Gessa G. L. (2003). Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine, the prototype atypical antipsychotic. Psychopharmacology, 167(1), 79–84
Khokhar J. Y., Henricks A. M., Sullivan E.D.K. & Green A.I. (2018). Unique Effects of Clozapine: A Pharmacological Perspective. Advances in Pharmacology (San Diego, Calif.), 82, 137–162
Lee C., Yang W. & Parr R. G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B, 37(2), 785–789
Perreault M. L., O’Dowd B.F. & George S.R. (2011). Dopamine receptor homooligomers and heterooligomers in schizophrenia. CNS Neuroscience & Therapeutics, 17(1), 52–7
Qin S., Hermans E. J., van Marle H.J.F., Luo J. & Fernández G. (2009). Acute Psychological Stress Reduces Working Memory-Related Activity in the Dorsolateral Prefrontal Cortex. Biological Psychiatry, 66(1), 25–32
Salmas R.E., Is Y.S., Durdagı S., Stein M. & Yurtsever M. (2018). A QM protein–ligand investigation of antipsychotic drugs with the dopamine D2 Receptor (D2R). Journal of Biomolecular Structure and Dynamics, 36, 2668-2677
Siskind D., McCartney L., Goldschlager R. & Kisely S. (2016). Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic rev