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New Approach to Anti-Anxiety Medication

Benzodiazepines (e.g., Valium) are fast-acting, effective anti-anxiety agents. However, they have side effects (sedation, tolerance development, and withdrawal symptoms) that can make them problematic for long-term use. Consequently, there is a need for medications that retain the rapid anti-anxiety effects of benzodiazepines, but lack their unfavorable side effects. Researchers have recently shown that a molecule called XBD173 might fill this bill. XBD173 is known to bind to the translocator protein (18 kD), formerly known as peripheral or mitochondrial benzodiazepine receptor. This translocator protein is believed to favor the production of certain neurosteroids that are potent positive modulators of GABA type A receptors that mediate the effects of the inhibitory neurotransmitter GABA in the mammalian nervous system. These neurosteroids produce pronounced anti-anxiety effects in animal models and their levels are reduced during panic attacks in humans with panic disorder. In the current work, the authors showed that XBD173 enhanced GABAergic neurotransmission and counteracted induced panic attacks in rodents, in the absence of sedation and tolerance development. XBD173 also exerted anti-panic activity in humans, and, in contrast to benzodiazepines, did not cause sedation and withdrawal symptoms. Therefore, the authors concluded that ligands of the translocator protein (18 kD) are promising candidates for fast-acting anti-anxiety drugs with less severe side effects than benzodiazepines. This work was published online on June 18 in Science Express. [Science abstract]