Facilitation of Social Support through Negative Allosteric Modulation of α5-Associated GABAA Receptors: A Novel Mechanism for the Treatment of Depression, Agitation, and Aggression in the Elderly

Abstract

Major depressive disorder is a highly-prevalent and debilitating disorder in the aged population. Accumulating clinical evidence suggests a key role for social support in helping to mitigate depression. Preclinical data are reviewed that indicate that selective negative allosteric modulation of 5-containing GABA A receptors, as with RY-080, might rapidly impact depression in patients. Further, preclinical data in transgenic mice modeling neurodegenerative diseases has suggested that this mechanism might also function to reduce agitation and aggression. These data are discussed in terms of the concept of