Benzodiazepine receptor ligands: a patent review (2006 -- 2012)

Introduction: Ligands at the benzodiazepine site of the GABAA receptor (GABAA-R) act by modulating the effect of GABAA (g-aminobutyric acid). The selective modulator effects of such ligands are related to the a-subunits type (i.e., a1, a2, a3, and a5), being shown that the a1 subunit is associated with sedative, anticonvulsant and amnesic effects; whereas the a2 and a3 subunits mediate anxiolytic and myorelaxant effects. Recently it was shown the involvement of a5 subunit in pain relief, which is involved in cognitive processes of learning and memory. Areas covered: This review covers patents, published from January 2006 to October 2012, on ligands for the benzodiazepine binding site of the GABAA-Rs. Patents filed from different companies and research groups report many series of compounds that may be used in the treatment or prevention of a large variety of neurodegenerative diseases. Expert opinion: Most patents highlighted that various memory deficits, related to Alzheimer’s disease, Down syndrome, mood disorders, schizophrenia, and age-related cognitive impairment may be treated using a5-selective ligands. Other aspects related to the use of allosteric modulators of the a7-nAchR and/or a5-GABAA-R (dual approach) for alleviating the impaired cognition and the use of a2-selective ligands for pain relief are highlighted, being particularly intriguing as new therapeutic approaches.