title: Identification of anxiolytic/nonsedative agents among indol-3-ylglyoxylamides acting as functionally selective agonists at the gamma-aminobutyric acid-A (GABAA) alpha2 benzodiazepine receptor.
abstract: Anxioselective agents may be identified among compounds binding selectively to the alpha(2)beta(x)gamma(2) subtype of the gamma-aminobutyric acid-A (GABA(A))/central benzodiazepine receptor (BzR) complex and behaving as agonists or among compounds binding with comparable potency to various BzR subtypes but eliciting agonism only at the alpha(2)beta(x)gamma(2) receptor. Because of subtle steric differences among BzR subtypes, the latter approach has proved much more successful. A biological screening within the class of indol-3-ylglyoxylamides 1-3 allowed us to identify compounds 1c and 2b as potential anxiolytic/nonsedative agents showing alpha(2) selective efficacy in vitro and anxioselective effects in vivo. According to molecular modeling studies, and consistently with SARs accumulated in the past decade, 5-NO(2)- and 5-H-indole derivatives would preferentially bind to BzR by placing the indole ring in the L(Di) and the L(2) receptor binding sites, respectively.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita di Pisa, Via Bonanno 6, 56126 Pisa, Italy. barbara.cosimelli@unina.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosimelli
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marini
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.forename: Francesca
authors.initials: F
authors.lastname: Simorini
authors.forename: Silvia
authors.initials: S
authors.lastname: Salerno
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Greco
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Salvetti
authors.forename: Gianluca
authors.initials: G
authors.lastname: L'Abbate
authors.forename: Silvia
authors.initials: S
authors.lastname: Trasciatti
authors.forename: Marina
authors.initials: M
authors.lastname: Montali
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D003198:Computer Simulation; D058785:GABA-A Receptor Agonists; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D058785:GABA-A Receptor Agonists