Science：“忘忧”蛋白

　　

生物通报道，德国Max-Planck研究所，等处的研究人员在Science在线版发表最新研究进展Translocator Protein (18 kDa) as Target for Anxiolytics without Benzodiazepine-Like Side Effects，解析一种能减轻生物体忧虑的蛋白。

 

据悉，一种大小为18kD的转运蛋白配体具有可消除小鼠及人力焦虑和惊恐的作用，这种蛋白被认为是一种具有前景的抗抑郁药物，与当前的Benzodiazepine样抗抑郁药物相比，这种新的蛋白不会引发严重的副作用。

 

这种转运蛋白配体被称为XBD173，研究小组在实验室中将这一蛋白用于大鼠实验中，他们观察到使用了XBD173后，大鼠的惊恐情绪可被很好的缓解过来，且没有产生不良副作用。

 

研究小组接着在70位健康男性身上做类似的研究，其中包括一组服用安慰剂的对照组。研究结果表明，XDB173能快速启动一种抗焦虑的生物学反应。XDB173主要通过调节抑制性的神经递质GABA来促进生物体产生镇静作用。研究小组正考虑将这一成果在临床上应用开来。

（生物通 小茜）

生物通推荐原文摘要：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.

【Abstract】

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.