Kim Yangsik, Kim Seyong
Department of Psychiatry, Inha University Hospital, Incheon, Republic of Korea.
Mental Health Rearch Institute, National Center for Mental Health, Seoul, Republic of Korea.
Psychiatry Investig. 2023 Jun;20(6):504-514. doi: 10.30773/pi.2022.0343. Epub 2023 May 30.
New drugs are needed to treat antipsychotic-resistant schizophrenia, especially those with clozapine-resistant schizophrenia. Atypical antipsychotics have predominantly 5-HT2A and dopaminergic antagonism, but also require investigation of other receptors.
In this study, the binding affinities between clozapine, olanzapine, and quetiapine with neuropharmacological, immunological, and metabolic receptors were measured using GNINA (Deep Learning Based Molecular Docking) and AlphaFold (Predicted Protein Structures).
Through this study, it was determined that these antipsychotics showed high binding affinity to a variety of receptors, such as CB2, 5-HT1BR, NPYR4, and CCR5. Cyclosporin A and everolimus which show high affinities with those receptors could be used for the development of new antipsychotic drugs based on these drugs.
In the future, the method used in this study will be applied to the development of new antipsychotic drugs, including drug repositioning, and to the discovery of the pathophysiology of schizophrenia.
需要新的药物来治疗对抗精神病药物耐药的精神分裂症，尤其是对氯氮平耐药的精神分裂症。非典型抗精神病药物主要具有5-羟色胺2A和多巴胺能拮抗作用，但也需要研究其他受体。
在本研究中，使用GNINA（基于深度学习的分子对接）和AlphaFold（预测蛋白质结构）测量了氯氮平、奥氮平和喹硫平与神经药理学、免疫学和代谢受体之间的结合亲和力。
通过本研究确定，这些抗精神病药物对多种受体表现出高结合亲和力，如CB2、5-羟色胺1B受体、神经肽Y受体4和趋化因子受体5。与这些受体具有高亲和力的环孢素A和依维莫司可用于基于这些药物开发新的抗精神病药物。
未来，本研究中使用的方法将应用于新抗精神病药物的开发，包括药物重新定位，以及精神分裂症病理生理学的发现。
