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Archive - Jun 18, 2009

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]

Merkel Cells Linked to Light-Touch Sensation

Scientists have demonstrated that the sensation of light touch, such as that which allows one to feel the fine texture of materials or lets the blind read Braille, depends on the activity of the long-mysterious Merkel cells, which are present in high numbers on our fingertips and lips. These cells form complexes with nerve fibers, and while these complexes are known to respond to light touches to the skin, the specific role of the Merkel cells has been controversial. The topic has been debated for more than 100 years, since the cells were first described in 1875 by German scientist Friedrich Merkel, who himself first proposed the link with light-touch sensation. The key to the current conclusive demonstration of the link was work with a transcription factor gene called Atoh1. When this gene was conditionally knocked out in the body skin and foot pads of mice, the resulting knockouts had no Merkel cells in these areas. The skin of these knockout mice did not show the same neurological responses to light touch that normal skin does, suggesting that Merkel cells enable their connecting neurons to resolve fine spatial details, the authors reported. "To our knowledge, Atoh1 is the first gene shown to be necessary for the specification of Merkel cells," the authors noted. "We don't know how any mammalian touch receptor works," added Dr. Ellen Lumpkin, of the Baylor College of Medicine, and a senior author on the report. "What genes allow them to function as light or painful touch receptors? This project gives us the experimental handle with which to start to dissect the genetic basis of touch." Among the other authors on the report were Dr. Huda Zoghbi and Dr. Stephen Maricich. This work was reported in the June 19 issue of Science. [Press release]