GABAA receptor subtype modulators in medicinal chemistry: an updated patent review (2014-present)

Introduction: Ligands at the benzodiazepine binding site of the GABAA receptor (GABAAR) act by modulating the effect of GABA (γ-aminobutyric acid). The benzodiazepine drugs are conventionally categorized as positive allosteric modulators enhancing the chloride ion current GABA-induced. In literature there are also reported ligands that act as negative allosteric modulators, reducing chloride ion current, and silent allosteric modulators not influencing the chloride ion flux. Areas covered: This review covers patents published from 2014 to present on ligands for the benzodiazepine binding site of the GABAARs. Patents filed from different companies and research groups report many compounds that may be used in the treatment/prevention of a large variety of diseases. Expert opinion: Since the discovery of the first benzodiazepine about 60 years have passed and about 50 years since the identification of their target, GABAA receptor. Even if benzodiazepines are the most popular anxiolytic drugs, the research in this field is still very active. From patents/application analysis arises that most of them claim methods for alleviating specific symptoms in different neurodegenerative diseases and their related memory deficits. Noteworthy is the presence of the α4- and α5-GABAA receptor subtype ligands as new pharmacological tools for airway hyperresponsiveness, inflammation diseases, and asthma.