Literature DB >> 28337332

BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia.

Dalton King1, Christiana Iwuagwu1, Jim Cook1, Ivar M McDonald1, Robert Mate1, F Christopher Zusi1, Matthew D Hill1, Haiquan Fang1, Rulin Zhao1, Bei Wang1, Amy E Easton1, Regina Miller1, Debra Post-Munson1, Ronald J Knox1, Lizbeth Gallagher1, Ryan Westphal1, Thaddeus Molski1, Jingsong Fan1, Wendy Clarke1, Yulia Benitex1, Kimberley A Lentz1, Rex Denton1, Daniel Morgan1, Robert Zaczek1, Nicholas J Lodge1, Linda J Bristow1, John E Macor1, Richard E Olson1.   

Abstract

The therapeutic treatment of negative symptoms and cognitive dysfunction associated with schizophrenia is a significant unmet medical need. Preclinical literature indicates that α7 neuronal nicotinic acetylcholine (nACh) receptor agonists may provide an effective approach to treating cognitive dysfunction in schizophrenia. We report herein the discovery and evaluation of 1c (BMS-933043), a novel and potent α7 nACh receptor partial agonist with high selectivity against other nicotinic acetylcholine receptor subtypes (>100-fold) and the 5-HT3A receptor (>300-fold). In vivo activity was demonstrated in a preclinical model of cognitive impairment, mouse novel object recognition. BMS-933043 has completed Phase I clinical trials.

Entities:  

Keywords:  Schizophrenia; clinical candidate; quinuclidine; α7 nAChR partial agonist; α7 neuronal nicotinic acetylcholine receptor

Year:  2017        PMID： 28337332      PMCID： PMC5346989          DOI： 10.1021/acsmedchemlett.7b00032

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  36 in total

1.  Immediate and sustained improvements in working memory after selective stimulation of α7 nicotinic acetylcholine receptors.

Authors:  Stacy A Castner; Gennady N Smagin; Timothy M Piser; Yi Wang; Jeffrey S Smith; Edward P Christian; Ladislav Mrzljak; Graham V Williams
Journal:  Biol Psychiatry       Date:  2010-10-20       Impact factor: 13.382

2.  (R)-3'-(3-methylbenzo[b]thiophen-5-yl)spiro[1-azabicyclo[2,2,2]octane-3,5'-oxazolidin]-2'-one, a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist displays cognitive enhancing properties.

Authors:  Ryo Tatsumi; Masakazu Fujio; Shin-ichi Takanashi; Atsushi Numata; Jiro Katayama; Hiroyuki Satoh; Yasuyuki Shiigi; Jun-ichi Maeda; Makoto Kuriyama; Takashi Horikawa; Takahiro Murozono; Kenji Hashimoto; Hiroshi Tanaka
Journal:  J Med Chem       Date:  2006-07-13       Impact factor: 7.446

3.  Desensitization characteristics of the human alpha7nAChR/5HT3A chimera receptor.

Authors:  Theo Dinklo; Anne S Lesage; Christopher G Grantham
Journal:  J Mol Neurosci       Date:  2006       Impact factor: 3.444

4.  Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms.

Authors:  Kristi A Sacco; Angelo Termine; Aisha Seyal; Melissa M Dudas; Jennifer C Vessicchio; Suchitra Krishnan-Sarin; Peter I Jatlow; Bruce E Wexler; Tony P George
Journal:  Arch Gen Psychiatry       Date:  2005-06

5.  EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors.

Authors:  Jos Prickaerts; Nick P van Goethem; Richard Chesworth; Gideon Shapiro; Frank G Boess; Christoph Methfessel; Olga A H Reneerkens; Dorothy G Flood; Dana Hilt; Maria Gawryl; Sonia Bertrand; Daniel Bertrand; Gerhard König
Journal:  Neuropharmacology       Date:  2011-11-10       Impact factor: 5.250

Review 6.  Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia.

Authors:  Jared W Young; Mark A Geyer
Journal:  Biochem Pharmacol       Date:  2013-07-12       Impact factor: 5.858

7.  Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).

Authors:  R Freedman; S Leonard; J M Gault; J Hopkins; C R Cloninger; C A Kaufmann; M T Tsuang; S V Farone; D Malaspina; D M Svrakic; A Sanders; P Gejman
Journal:  Am J Med Genet       Date:  2001-01-08

8.  Selective alpha7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes.

Authors:  Simon Sydserff; E J Sutton; Dekun Song; Michael C Quirk; Carla Maciag; Chaoying Li; Gerald Jonak; David Gurley; John C Gordon; Edward P Christian; James J Doherty; Tom Hudzik; Edwin Johnson; Ladislav Mrzljak; Tim Piser; Gennady N Smagin; Yi Wang; Dan Widzowski; Jeffrey S Smith
Journal:  Biochem Pharmacol       Date:  2009-07-16       Impact factor: 5.858

9.  A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia.

Authors:  Jeffrey A Lieberman; Geoffrey Dunbar; Anthony C Segreti; Ragy R Girgis; Frances Seoane; Jessica S Beaver; Naihua Duan; David A Hosford
Journal:  Neuropsychopharmacology       Date:  2012-12-18       Impact factor: 7.853

10.  α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer's Disease.

Authors:  Jun Toyohara; Kenji Hashimoto
Journal:  Open Med Chem J       Date:  2010-05-27
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  3 in total

Review 1.  Schizophrenia: synthetic strategies and recent advances in drug design.

Authors:  Maria Azmanova; Anaïs Pitto-Barry; Nicolas P E Barry
Journal:  Medchemcomm       Date:  2018-03-16       Impact factor: 3.597

2.  Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning.

Authors:  Michael R Weed; Joseph Polino; Laura Signor; Mark Bookbinder; Deborah Keavy; Yulia Benitex; Daniel G Morgan; Dalton King; John E Macor; Robert Zaczek; Richard Olson; Linda J Bristow
Journal:  PLoS One       Date:  2017-12-19       Impact factor: 3.240

Review 3.  Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors.

Authors:  Roger L Papke; Nicole A Horenstein
Journal:  Pharmacol Rev       Date:  2021-07       Impact factor: 18.923
  3 in total

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