An Inverse Agonist Selective for α5 Subunit-Containing GABAA Receptors Enhances Cognition
@article{Dawson2006AnIA, title={An Inverse Agonist Selective for α5 Subunit-Containing GABAA Receptors Enhances Cognition}, author={G. R. Dawson and K. Maubach and N. Collinson and M. Cobain and B. Everitt and A. Macleod and H. Choudhury and L. McDonald and G. Pillai and W. Rycroft and A. Smith and F. Sternfeld and F. Tattersall and K. Wafford and D. Reynolds and G. Seabrook and J. Atack}, journal={Journal of Pharmacology and Experimental Therapeutics}, year={2006}, volume={316}, pages={1335 - 1345} }
α5IA is a compound that binds with equivalent subnanomolar affinity to the benzodiazepine (BZ) site of GABAA receptors containing an α1, α2, α3, or α5 subunit but has inverse agonist efficacy selective for the α5 subtype. As a consequence, the in vitro and in vivo effects of this compound are mediated primarily via GABAA receptors containing an α5 subunit. In a mouse hippocampal slice model, α5IA significantly enhanced the θ burst-induced long-term potentiation of the excitatory postsynaptic… CONTINUE READING
Figures, Tables, and Topics from this paper
208 Citations
RO4938581, a novel cognitive enhancer acting at GABAA α5 subunit-containing receptors
- Psychology, Medicine
- Psychopharmacology
- 2008
- 142
- Highly Influenced
Preclinical and clinical pharmacology of the GABAA receptor alpha5 subtype-selective inverse agonist alpha5IA.
- Medicine
- Pharmacology & therapeutics
- 2010
- 85
GABAA Receptor α2/α3 Subtype-Selective Modulators as Potential Nonsedating Anxiolytics
- Medicine
- 2009
- 42
L-655,708 enhances cognition in rats but is not proconvulsant at a dose selective for α5-containing GABAA receptors
- Chemistry, Medicine
- Neuropharmacology
- 2006
- 155
- PDF
Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice
- Psychology, Medicine
- Journal of psychopharmacology
- 2011
- 144
- Highly Influenced
An inverse agonist selective for α5 subunit-containing GABAA receptors improves encoding and recall but not consolidation in the Morris water maze
- Psychology, Medicine
- Psychopharmacology
- 2006
- 92
- PDF
PWZ-029, a compound with moderate inverse agonist functional selectivity at GABAA receptors containing α5 subunits, improves passive, but not active, avoidance learning in rats
- Chemistry, Medicine
- Brain Research
- 2008
- 54
- Highly Influenced
- PDF
Selective Modulators of α5-Containing GABAA Receptors and their Therapeutic Significance.
- Medicine
- Current drug targets
- 2015
- 18
- PDF
Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist
- Chemistry, Medicine
- Journal of psychopharmacology
- 2011
- 43
MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans
- Chemistry, Medicine
- Journal of psychopharmacology
- 2011
- 48
- PDF
References
SHOWING 1-10 OF 64 REFERENCES
Trace fear conditioning involves hippocampal α5 GABAA receptors
- Biology
- Proceedings of the National Academy of Sciences of the United States of America
- 2002
- 463
- PDF
Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes
- Biology
- Nature
- 1999
- 1,029
- Highly Influential
Effects of Hippocampal Injections of a Novel Ligand Selective for the α5β2γ2 Subunits of the GABA/Benzodiazepine Receptor on Pavlovian Conditioning
- Psychology
- Neurobiology of Learning and Memory
- 2002
- 37
- PDF
Modulation of Long-term Potentiation in CA1 Region of Mouse Hippocampal Brain Slices by GABAA Receptor Benzodiazepine Site Ligands
- Chemistry, Medicine
- Neuropharmacology
- 1997
- 76
Anxiogenic properties of an inverse agonist selective for α3 subunit‐containing GABAA receptors
- Chemistry
- 2005
- 110
Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the α5 Subunit of the GABAAReceptor
- Chemistry, Medicine
- The Journal of Neuroscience
- 2002
- 557
- PDF
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
- Chemistry, Medicine
- European Neuropsychopharmacology
- 2002
- 21
Regional Differences in the Inhibition of Mouse In Vivo [3H]Ro 15-1788 Binding Reflect Selectivity for α1 versus α2 and α3 Subunit-Containing GABAA Receptors
- Chemistry
- Neuropsychopharmacology
- 1999
- 53
- PDF
Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics.
- Biology, Medicine
- Annual review of pharmacology and toxicology
- 2004
- 508
Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor α1 subtype
- Chemistry, Medicine
- Nature Neuroscience
- 2000
- 862