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Published Online June 18, 2009
Science DOI: 10.1126/science.1175055

Reports

Submitted on April 16, 2009
Accepted on June 8, 2009

Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects

Rainer Rupprecht 1*, Gerhard Rammes 2, Daniela Eser 3, Thomas C. Baghai 3, Cornelius Schüle 3, Caroline Nothdurfter 1, Thomas Troxler 4, Conrad Gentsch 4, Hans O. Kalkman 4, Frederique Chaperon 4, Veska Uzunov 4, Kevin H. McAllister 4, Valerie Bertaina-Anglade 5, Christophe Drieu La Rochelle 5, Dietrich Tuerck 6, Annette Floesser 4, Beate Kiese 7, Michael Schumacher 8, Rainer Landgraf 9, Florian Holsboer 9, Klaus Kucher 4

1 Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, Munich, 80336 Germany.; Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2, Munich, 80804 Germany.
2 Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2, Munich, 80804 Germany.; Department of Anaesthesiology, Technische Universität, Munich, Germany.
3 Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, Munich, 80336 Germany.
4 Novartis Institute for Biomedical Research (NIBR), Neuroscience, Basel, Switzerland.
5 Biotrial, Rennes, France.
6 DMPK, F. Hoffmann-La Roche AG, Basel, Switzerland.
7 Biostatistics, Novartis Pharma AG, Basel, Switzerland.
8 INSERM UMR 788, Paris, France.
9 Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2, Munich, 80804 Germany.

* To whom correspondence should be addressed.
Rainer Rupprecht , E-mail: Rainer.Rupprecht{at}med.uni-muenchen.de

Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by development of tolerance and withdrawal symptoms. Ligands of the translocator protein (18 kD) may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models. Here, we found that the translocator protein (18 kD) ligand XBD173 enhanced GABAergic neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation and withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A New and Improved Anxiolytic?.
(2009)
Journal Watch (General) 2009, 3
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Science. ISSN 0036-8075 (print), 1095-9203 (online)