GABA_A Receptor Ligands Often Interact with Binding Sites in the Transmembrane Domain and in the Extracellular Domain-Can the Promiscuity Code Be Cracked?

ABSTRACT: Many allosteric binding sites that modulate gamma aminobutyric acid (GABA) effects have been described in heteropentameric GABA type A (GABA_A) receptors, among them sites for benzodiazepines, pyrazoloquinolinones and etomidate. Diazepam not only binds at the high affinity extracellular "canonical" site, but also at sites in the transmembrane domain. Many ligands of the benzodiazepine binding site interact also with homologous sites in the extracellular domain, among them the pyrazoloquinolinones that exert modulation at extracellular α+/β- sites. Additional interaction of this chemotype with the sites for etomidate has also been described. We have recently described a new indole-based scaffold with pharmacophore features highly similar to pyrazoloquinolinones as a novel class of

SUBMITTER: Iorio MT 

PROVIDER: S-EPMC6982053 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature