title: Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects.
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 the development of tolerance and withdrawal symptoms. Ligands of the translocator protein [18 kilodaltons (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 gamma-aminobutyric acid-mediated 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 or withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines.
authors: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, Munich 80336, Germany. rainer.rupprecht@med.uni-muenchen.de
authors: Rainer
authors: R
authors: Rupprecht
authors: Gerhard
authors: G
authors: Rammes
authors: Daniela
authors: D
authors: Eser
authors: Thomas C
authors: TC
authors: Baghai
authors: Cornelius
authors: C
authors: Schüle
authors: Caroline
authors: C
authors: Nothdurfter
authors: Thomas
authors: T
authors: Troxler
authors: Conrad
authors: C
authors: Gentsch
authors: Hans O
authors: HO
authors: Kalkman
authors: Frederique
authors: F
authors: Chaperon
authors: Veska
authors: V
authors: Uzunov
authors: Kevin H
authors: KH
authors: McAllister
authors: Valerie
authors: V
authors: Bertaina-Anglade
authors: Christophe Drieu
authors: CD
authors: La Rochelle
authors: Dietrich
authors: D
authors: Tuerck
authors: Annette
authors: A
authors: Floesser
authors: Beate
authors: B
authors: Kiese
authors: Michael
authors: M
authors: Schumacher
authors: Rainer
authors: R
authors: Landgraf
authors: Florian
authors: F
authors: Holsboer
authors: Klaus
authors: K
authors: Kucher
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000378:metabolism*; D001569:Benzodiazepines / Q000009:adverse effects; D002460:Cell Line; D004361:Drug Tolerance; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000378:metabolism; D016584:Panic Disorder / Q000188:drug therapy; D011687:Purines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control; D013758:Tetragastrin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D007546:Isoquinolines; C502525:N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D018377:Neurotransmitter Agents; D011687:Purines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C499229:TSPO protein, human; D013758:Tetragastrin; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; C037850:PK 11195; D000525:Alprazolam