Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design

Abstract

Due to high oxygen consumption, the brain is particularly vulnerable to oxidative stress, which is considered an important element in the etiopathogenesis of several mental disorders, including schizophrenia, depression and dependencies. Despite the fact that it is not established yet whether oxidative stress is a cause or a consequence of clinic manifestations, the intake of antioxidant supplements in combination with the psychotropic therapy constitutes a valuable solution in patients’ treatment. Anyway, some drugs possess antioxidant capacity themselves and this aspect is discussed in this review, focusing on antipsychotics and antidepressants. In the context of a collection of clinical observations, in vitro and in vivo results are critically reported, often highlighting controversial aspects. Finally, a new challenge is discussed, i.e., the possibility of assessing in silico the antioxidant potential of these drugs, exploiting computational chemistry methodologies and machine learning. Despite the physiological environment being incredibly complex and the detection of meaningful oxidative stress biomarkers being all but an easy task, a rigorous and systematic analysis of the structural and reactivity properties of antioxidant drugs seems to be a promising route to better interpret therapeutic outcomes and provide elements for the rational design of novel drugs.

Selenoxide Elimination Triggers Enamine Hydrolysis to Primary and Secondary Amines: A Combined Experimental and Theoretical Investigation

“…This substrate was chosen as a model also because the corresponding elimination product, morpholine, represents an outstanding example of pharmacologically relevant moiety. Interestingly, it can be found in drugs acting on CNS (e.g., in the antidepressants reboxetine and viloxazine and in the withdrawn stimulant phenmetrazine), and which are used to treat pathologies where oxidative stress has been demonstrated to play a role on disease onset and progression [ 28 , 29 ]. More in detail, compound 3 was dissolved in deuterated water and reacted with 1.2 equivalents of hydrogen peroxide at room temperature.…”

A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration

“…The presence of several mechanisms is perfectly in harmony with the growing interest towards the development of multi-target-directed ligands (MTDL) that take advantage of synergistic pharmacological effects [ 62 ]. Moreover, depending on their chemical structures, the neuroprotective effect of several natural and nature-inspired compounds, as outlined above, is also connected with their activity against reactive oxygen species (ROS) and inflammation [ 63 , 64 , 65 , 66 ]. In this connection, it was also reported that natural PDE inhibitors, by increasing cGMP levels, reduce the production of IL-6 and TNF-α [ 23 ].…”

Lithium and Atypical Antipsychotics: The Possible WNT/β Pathway Target in Glaucoma

“…This suggests that risperidone and other AAPs can decrease OS in glaucoma [ 148 , 152 ]. Among AAPs, clozapine and olanzapine can also decrease OS [ 148 , 153 ]. Nevertheless, few studies have investigated the relationship between AAPs and the WNT/β-catenin pathway in glaucoma by acting OS and thus, the ROS production.…”