The role of nitric oxide (NO) donors in anxiety. Lights and shadows.

Anxiety-related disorders are a common public health issues. Current medication for this affective disorder involves the GABA-ergic or the serotonergic transmission. Different forms of anxiety, however, are resistant to treatment with GABA-ergic or serotonergic agents and the use of these compounds can be associated with severe side effects. Thus, almost 60 years after the discovery of the benzodiazepines there is need not only for fresh medications but also alternative targets. The nitrergic system has emerged as a promising target since several lines of evidence suggest that nitric oxide (NO), an intra- and inter-cellular messenger in the brain, is implicated in anxiety. Therefore, NO modulators might be beneficial. Here I critically review advances in research of agents acting on the nitrergic system, such as the NO donors, for the treatment of anxiety. Present analysis suggests that although NO donors are involved in anxiety their potential anxiolytic effect remains to be established.