Abstract
(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (13) has been identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors. 13 is orally bioavailable, readily penetrates the CNS, and enhances performance in animal models of cognition. It does not exhibit the convulsant, proconvulsant, or anxiogenic activity associated with nonselective GABA(A) inverse agonists.
MeSH terms
-
Administration, Oral
-
Animals
-
Binding Sites
-
Biological Availability
-
Cognition / drug effects*
-
Dogs
-
GABA-A Receptor Agonists*
-
Isoxazoles / adverse effects
-
Isoxazoles / chemical synthesis*
-
Isoxazoles / pharmacology
-
Maze Learning / drug effects
-
Mice
-
Nootropic Agents / adverse effects
-
Nootropic Agents / chemical synthesis*
-
Nootropic Agents / pharmacology
-
Patch-Clamp Techniques
-
Protein Subunits
-
Radioligand Assay
-
Rats
-
Receptors, GABA-A / metabolism
-
Triazines / adverse effects
-
Triazines / chemical synthesis*
-
Triazines / pharmacology
Substances
-
GABA-A Receptor Agonists
-
Isoxazoles
-
MRK 016
-
Nootropic Agents
-
Protein Subunits
-
Receptors, GABA-A
-
Triazines