Literature DB >> 19762240

The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction.

Henner Knust1, Guido Achermann, Theresa Ballard, Bernd Buettelmann, Rodolfo Gasser, Holger Fischer, Maria-Clemencia Hernandez, Frédéric Knoflach, Andreas Koblet, Heinz Stadler, Andrew W Thomas, Gerhard Trube, Pius Waldmeier.   

Abstract

Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABAA alpha5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models.

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Year:  2009        PMID： 19762240     DOI： 10.1016/j.bmcl.2009.08.053

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  9 in total

1.  α5GABAA subunit-containing receptors and sweetened alcohol cue-induced reinstatement and active sweetened alcohol self-administration in male rats.

Authors:  Cassie M Chandler; Jaren Reeves-Darby; Sherman A Jones; J Abigail McDonald; Guanguan Li; Md T Rahman; James M Cook; Donna M Platt
Journal:  Psychopharmacology (Berl)       Date:  2019-01-12       Impact factor: 4.530

2.  Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats.

Authors:  John P Redrobe; Lisbeth Elster; Kristen Frederiksen; Christoffer Bundgaard; Inge E M de Jong; Garrick P Smith; Anne Techau Bruun; Peter H Larsen; Michael Didriksen
Journal:  Psychopharmacology (Berl)       Date:  2011-11-29       Impact factor: 4.530

Review 3.  GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia.

Authors:  Meng-Yi Xu; Albert H C Wong
Journal:  Acta Pharmacol Sin       Date:  2018-03-22       Impact factor: 6.150

Review 4.  GABAA receptor subtypes: Therapeutic potential in Down syndrome, affective disorders, schizophrenia, and autism.

Authors:  Uwe Rudolph; Hanns Möhler
Journal:  Annu Rev Pharmacol Toxicol       Date:  2013-10-23       Impact factor: 13.820

Review 5.  Disinhibition, an emerging pharmacology of learning and memory.

Authors:  Hanns Möhler; Uwe Rudolph
Journal:  F1000Res       Date:  2017-02-03

6.  Quercetin Reduces Cortical GABAergic Transmission and Alleviates MK-801-Induced Hyperactivity.

Authors:  Hui-Ran Fan; Wei-Feng Du; Tao Zhu; Yan-Jiao Wu; Yan-Mei Liu; Qi Wang; Qin Wang; Xue Gu; Xingyue Shan; Shining Deng; Tailin Zhu; Tian-Le Xu; Wei-Hong Ge; Wei-Guang Li; Fei Li
Journal:  EBioMedicine       Date:  2018-07-26       Impact factor: 8.143

7.  Tricyclic antipsychotics and antidepressants can inhibit α5-containing GABAA receptors by two distinct mechanisms.

Authors:  Konstantina Bampali; Filip Koniuszewski; Luca L Silva; Sabah Rehman; Florian D Vogel; Thomas Seidel; Petra Scholze; Florian Zirpel; Arthur Garon; Thierry Langer; Matthäus Willeit; Margot Ernst
Journal:  Br J Pharmacol       Date:  2022-03-07       Impact factor: 9.473

8.  Extrasynaptic GABA(A) receptors: their function in the CNS and implications for disease.

Authors:  Stephen G Brickley; Istvan Mody
Journal:  Neuron       Date:  2012-01-12       Impact factor: 17.173

Review 9.  Implications of GABAergic Neurotransmission in Alzheimer's Disease.

Authors:  Yanfang Li; Hao Sun; Zhicai Chen; Huaxi Xu; Guojun Bu; Hui Zheng
Journal:  Front Aging Neurosci       Date:  2016-02-23       Impact factor: 5.750
  9 in total

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