L-655,708 enhances cognition in rats but is not proconvulsant at a dose selective for α5-containing GABAA receptors

@article{Atack2006L655708EC,
  title={L-655,708 enhances cognition in rats but is not proconvulsant at a dose selective for $\alpha$5-containing GABAA receptors},
  author={J. Atack and P. Bayley and G. Seabrook and K. Wafford and R. Mckernan and G. Dawson},
  journal={Neuropharmacology},
  year={2006},
  volume={51},
  pages={1023-1029}
}
The in vitro and in vivo properties of L-655,708, a compound with higher affinity for GABA(A) receptors containing an alpha5 compared to an alpha1, alpha2 or alpha3 subunit have been examined further. This compound has weak partial inverse agonist efficacy at each of the four subtypes but, and consistent with the binding data, has higher functional affinity for the alpha5 subtype. In a mouse hippocampal slice model, L-655,708 was able to enhance the long-term potentiation produced by a theta… Expand
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In mice and rats, in vitro data suggesting that α5IA may enhance cognition without being proconvulsant were confirmed, and in vivo rodent models suggest that the GABAA α5-subtype provides a novel target for the development of selective inverse agonists with utility in the treatment of disorders associated with a cognitive deficit. Expand
Behavioral profile of L-655,708, a selective ligand for the benzodiazepine site of GABA-A receptors which contain the α5 subunit, in social encounters between male mice
GABA-A receptor is a transmembrane hetero-oligomeric protein which consists of five subunits, the combination of which confers unique pharmacological properties to the receptor. It is well-known thatExpand
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
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Results indicate that L-655,708 could exhibit an anxiogenic-like profile in the elevated plus-maze test, and this ligand is selective for GABA(A) receptors containing an alpha-5 subunit, a region which has been involved in the modulation of anxiety. Expand
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
GABAA receptor is a transmembrane hetero-oligomeric protein which consists of five subunits, the combination of which confers unique pharmacological properties to the receptor. L-655,708 is a newExpand
In vivo labelling of α5 subunit-containing GABAA receptors using the selective radioligand [3H]L-655,708
L-655,708 is an imidazobenzodiazepine possessing 30-70-fold selectivity for the benzodiazepine binding site of GABA(A) receptors containing an alpha5 rather than alpha1, alpha2 or alpha3 subunit. InExpand
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It is shown that RY-080 possesses inverse agonism for the alpha1 and alpha5 subtypes of human recombinant GABAA receptors and whilst not convulsant it was pro Convulsant and accordingly the proconvulsant effects of Ry-080 cannot be attributed solely to thealpha5 subtype. Expand
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