Synthesis, in vitro affinity, and efficacy of a bis 8-ethynyl-4H-imidazo[1,5a]- [1,4]benzodiazepine analogue, the first bivalent alpha5 subtype selective BzR/GABA(A) antagonist.
The synthesis and in vitro affinity of the alpha5beta3gamma2 (alpha5) subtype selective BzR/GABA(A) antagonist 7 is described. This ligand is selective for alpha5 subtypes in vitro and is a potent antagonist of the effects of diazepam only at alpha5beta3gamma2 subtypes (oocytes). Ligands such as 7 will be important in the determination of which physiological function(s) are subserved by this GABA(A) alpha5 subtype.
Li
Xiaoyan
X
Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
Cao
Hui
H
Zhang
Chunchun
C
Furtmueller
Roman
R
Fuchs
Karoline
K
Huck
Sigismund
S
Sieghart
Werner
W
Deschamps
Jeffrey
J
Cook
James M
JM
D000818:Animals; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D018360:Crystallography, X-Ray; D018756:GABA Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000502:physiology; D013329:Structure-Activity Relationship; D014981:Xenopus
C480603:1,3-bis(8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine-3-carboxy)propyl diester; D001570:Benzodiazepinones; D018118:Chloride Channels; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D007093:Imidazoles; D008024:Ligands; D011963:Receptors, GABA-A