Selective, orally active gamma-aminobutyric acid(A) alpha 5 receptor inverse agonists as cognition enhancers

Nonselective inverse agonists at the gamma-aminobutyric acid(A) (GABA-A) benzodiazepine binding site have cognition-enhancing effects in animals but are anxiogenic and can precipitate convulsions. Herein, we describe novel GABA-A alpha5 subtype inverse agonists leading to the identification of 16 as...

Full description

Saved in:
Bibliographic Details
Published inJournal of medicinal chemistry Vol. 47; no. 9; pp. 2176 - 2179
Main Authors Sternfeld, F, Carling, RW, Jelley, RA, Ladduwahetty, T, Merchant, KJ, Moore, KW, Reeve, AJ, Street, LJ, O'Connor, D, Sohal, B, Atack, Cook, S, Seabrook, G, Wafford, K, Tattersall, FD, Collinson, N, Dawson, GR, Castro, JL, MacLeod, AM
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 22.04.2004
Subjects
Chemistry, Medicinal
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
SUBTYPES
AFFINITY
ANXIETY
PHARMACOLOGY
RAT-BRAIN
LIGAND
ALPHA-5-BETA-3-GAMMA-2
BENZODIAZEPINE-RECEPTOR
CONTAINING GABA(A) RECEPTORS
SUBUNIT
Online AccessGet full text

Cover

More Information
Summary:Nonselective inverse agonists at the gamma-aminobutyric acid(A) (GABA-A) benzodiazepine binding site have cognition-enhancing effects in animals but are anxiogenic and can precipitate convulsions. Herein, we describe novel GABA-A alpha5 subtype inverse agonists leading to the identification of 16 as an orally active, functionally selective compound that enhances cognition in animals without anxiogenic or convulsant effects. Compounds of this type may be useful in the symptomatic treatment of memory impairment associated with Alzheimer's disease and related dementias.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm031076j