New molecular targets for antianxiety interventions.

Recent advances in neuroscience and understanding in the etiology of anxiety have led researchers to new targets for treatments that are proving to be at least as effective as benzodiazepines, which have been the traditional treatment for anxiety for over 40 years. The gamma-aminobutyric acid (GABA) system has long been targeted in anxiety interventions via benzodiazepines, but better understanding of its role in anxiety disorders has led to the development of partial benzodiazepine-GABA receptor antagonists and agents that target specific subunits of the GABA-A receptor and that manipulate GABA levels. The recognition that antidepressants are effective in anxiety even in nondepressed patients has caused researchers to develop antianxiety agents that affect the serotonin and norepinephrine systems. Other neurotransmitter systems such as corticotropin-releasing factor and substance P appear to be abnormally regulated in patients with anxiety disorders, so antagonists of these neurotransmitters may prove to be beneficial anxiolytics. Meanwhile, antistress and antianxiety effects through neurogenesis may be possible with the use of agents that decrease glutamate neurotransmission, such as metabotropic glutamate receptor agonists. Finally, the stimulation of neurotrophic factors, such as brain-derived neurotrophic factor, which appears to enhance neurogenesis, may also prove to have anxiolytic effects.