Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder,
schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are
unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in
their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of
the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the
oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced
and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free
radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association
between an increased activity of XO and diverse mental diseases including depression or schizophrenia.
Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO
activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition
by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the
chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational
methods to design specific inhibitors with the capability of modulating XO activity.