Maria Sklodowska-Curie Medical Academy in Warsaw, Solidarnosci 12 Str., 03-411 Warsaw, Poland.
Military Institute of Hygiene and Epidemiology, 4 Kozielska Str., 01-163 Warsaw, Poland.
Int J Mol Sci. 2022 Mar 29;23(7):3739. doi: 10.3390/ijms23073739.
Mental health problems cover a wide spectrum of diseases, including mild to moderate anxiety, depression, alcohol/drug use disorders, as well as bipolar disorder and schizophrenia. Pharmacological treatment seems to be one of the most effective opportunities to recover function efficiently and satisfactorily. However, such disorders are complex as several target points are involved. This results in a necessity to combine different types of drugs to obtain the necessary therapeutic goals. There is a need to develop safer and more effective drugs. Considering that mental illnesses share multifactorial processes, the paradigm of one treatment with multiple modes of action rather than single-target strategies would be more effective for successful therapies. Therefore, hybrid molecules that combine two pharmacophores in one entity show promise, as they possess the desired therapeutic index with a small off-target risk. This review aims to provide information on chimeric structures designed for mental disorder therapy (i.e., schizophrenia and depression), and new types of drug candidates currently being tested. In addition, a discussion on some benefits and limitations of multifunctional, bivalent drug candidates is also given.
心理健康问题涵盖了广泛的疾病，包括轻度至中度焦虑、抑郁、酒精/药物使用障碍以及双相情感障碍和精神分裂症。药物治疗似乎是高效、满意地恢复功能的最有效机会之一。然而，由于涉及多个靶点，这些疾病非常复杂。这导致需要结合不同类型的药物来达到必要的治疗目标。因此，需要开发更安全、更有效的药物。鉴于精神疾病具有多因素的发病过程，一种药物具有多种作用模式而不是单一靶点的策略，对于成功的治疗更为有效。因此，将两种药效团结合在一个实体中的杂合分子具有很大的发展潜力，因为它们具有所需的治疗指数，且脱靶风险较小。本综述旨在提供用于治疗精神障碍（即精神分裂症和抑郁症）的嵌合体结构的信息，以及目前正在测试的新型候选药物。此外，还讨论了多功能、双价候选药物的一些优点和局限性。
