Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit.

[1]  B. Yee,et al.  A Pharmacogenetic ‘Restriction-of-Function’ Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by α5-Containing GABAA Receptors in Mice , 2016, Neuropsychopharmacology.

[2]  C. Kaczorowski,et al.  A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model , 2015, International journal of medicinal chemistry.

[3]  Andreas Lüthi,et al.  Regulating anxiety with extrasynaptic inhibition , 2015, Nature Neuroscience.

[4]  J. Lynch,et al.  Selective Modulators of α5-Containing GABAA Receptors and their Therapeutic Significance. , 2015, Current drug targets.

[5]  N. Harrison,et al.  Selective targeting of the α5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling. , 2015, American journal of physiology. Lung cellular and molecular physiology.

[6]  B. Roth,et al.  Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects , 2014, Brain Research.

[7]  U. Rudolph,et al.  GABAA receptor subtypes: Therapeutic potential in Down syndrome, affective disorders, schizophrenia, and autism. , 2014, Annual review of pharmacology and toxicology.

[8]  P. Soto,et al.  Allosteric Modulation of GABAA Receptor Subtypes: Effects on Visual Recognition and Visuospatial Working Memory in Rhesus Monkeys , 2013, Neuropsychopharmacology.

[9]  G. Guerrini,et al.  Benzodiazepine receptor ligands: a patent review (2006 – 2012) , 2013, Expert opinion on therapeutic patents.

[10]  Declan Murphy,et al.  The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: A pilot [11C]Ro15-4513 positron emission tomography study , 2013, Neuropharmacology.

[11]  B. Antkowiak,et al.  Enhancing the function of alpha5-subunit-containing GABAA receptors promotes action potential firing of neocortical neurons during up-states. , 2013, European journal of pharmacology.

[12]  M. Gallagher,et al.  Selective GABAA α5 positive allosteric modulators improve cognitive function in aged rats with memory impairment , 2013, Neuropharmacology.

[13]  P. Skolnick.  Anxioselective anxiolytics: on a quest for the Holy Grail. , 2012, Trends in pharmacological sciences.

[14]  C. Bundgaard,et al.  Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats , 2012, Psychopharmacology.

[15]  J. Cook,et al.  The role of &agr;1 and &agr;5 subunit-containing GABAA receptors in motor impairment induced by benzodiazepines in rats , 2012, Behavioural pharmacology.

[16]  M. Caron,et al.  Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy. , 2012, ACS chemical neuroscience.

[17]  A. Grace,et al.  A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia , 2011, Neuropsychopharmacology.

[18]  J. Atack,et al.  GABAA receptor subtype-selective modulators. II. α5-selective inverse agonists for cognition enhancement. , 2011, Current topics in medicinal chemistry.

[19]  G. Bormans,et al.  MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans , 2011, Journal of psychopharmacology.

[20]  B. Roth,et al.  Anxiolytic-like effects of 8-acetylene imidazobenzodiazepines in a rhesus monkey conflict procedure , 2010, Neuropharmacology.

[21]  W. Sieghart,et al.  The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. , 2010, European journal of pharmacology.

[22]  J. Cook,et al.  The differential role of alpha1- and alpha5-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats. , 2009, The international journal of neuropsychopharmacology.

[23]  J. Atack.  GABAA Receptor α2/α3 Subtype-Selective Modulators as Potential Nonsedating Anxiolytics , 2009 .

[24]  Kay Brune,et al.  Reversal of pathological pain through specific spinal GABAA receptor subtypes , 2008, Nature.

[25]  R. Borchardt,et al.  Enzymes involved in the bioconversion of ester-based prodrugs. , 2006, Journal of pharmaceutical sciences.

[26]  N Collinson,et al.  An Inverse Agonist Selective for α5 Subunit-Containing GABAA Receptors Enhances Cognition , 2006, Journal of Pharmacology and Experimental Therapeutics.

[27]  N. Bodor,et al.  Designing safer (soft) drugs by avoiding the formation of toxic and oxidative metabolites , 2004, Molecular biotechnology.

[28]  K. Maubach.  GABA(A) receptor subtype selective cognition enhancers. , 2003, Current drug targets. CNS and neurological disorders.

[29]  E. Burón,et al.  Anxiogenic-like activity of L-655,708, a selective ligand for the benzodiazepine site of GABAA receptors which contain the alpha-5 subunit, in the elevated plus-maze test , 2002, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[30]  F. García,et al.  Anxiogenic-like activity of L-655,708, a selective ligand for the benzodiazepine site of GABAA receptors which contain the alpha-5 subunit, in the elevated-plus maze test , 2002, European Neuropsychopharmacology.

[31]  F. Kuenzi,et al.  Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the α5 Subunit of the GABAAReceptor , 2002, The Journal of Neuroscience.

[32]  K. Vogt,et al.  Trace fear conditioning involves hippocampal α5 GABAA receptors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[33]  W. Mapleson,et al.  Tissue/blood and tissue/water partition coefficients for propofol in sheep. , 2001, British journal of anaesthesia.

[34]  R. Mckernan,et al.  Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor α1 subtype , 2000, Nature Neuroscience.

[35]  K Hirano,et al.  Hydrolytic profile for ester- or amide-linkage by carboxylesterases pI 5.3 and 4.5 from human liver. , 1997, Biological & pharmaceutical bulletin.

[36]  F. Stephenson,et al.  The GABAA receptors. , 1995, The Biochemical journal.

[37]  H. Okayama,et al.  High-efficiency transformation of mammalian cells by plasmid DNA. , 1987, Molecular and cellular biology.

[38]  J. Saavedra,et al.  Esophageal carcinogenesis in F344 rats by nitrosomethylethylamines substituted in the ethyl group. , 1982, Journal of the National Cancer Institute.

[39]  Y. Cheng,et al.  Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. , 1973, Biochemical pharmacology.

[40]  P. Soto,et al.  Allosteric Modulation of GABAA Receptor Subtypes: Effects on Visual Recognition and Visuospatial Working Memory in Rhesus Monkeys , 2013, Neuropsychopharmacology.

[41]  B. Roth,et al.  Novel positive allosteric modulators of GABAA receptors: do subtle differences in activity at alpha1 plus alpha5 versus alpha2 plus alpha3 subunits account for dissimilarities in behavioral effects in rats? , 2010, Progress in Neuro-psychopharmacology and Biological Psychiatry.

[42]  J. Atack.  GABAA receptor alpha2/alpha3 subtype-selective modulators as potential nonsedating anxiolytics. , 2010, Current topics in behavioral neurosciences.

[43]  W. Sieghart,et al.  Are GABAA Receptors Containing α5 Subunits Contributing to the Sedative Properties of Benzodiazepine Site Agonists? , 2008, Neuropsychopharmacology.

[44]  K. Vogt,et al.  Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors. , 2002, Proceedings of the National Academy of Sciences of the United States of America.