Synthesis, in Vitro Affinity, and Efficacy of a Bis 8-Ethynyl-4H-imidazo[1,5a]- [1,4]benzodiazepine Analogue, the First Bivalent α5 Subtype Selective BzR/GABAAAntagonist

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.