Neuropharmacology of Non-benzodiazepine Anxiolytics and Sedatives

The development of non-benzodiazepine drugs that have only the anxiolytic or sedative action of benzodiazepines started in the latter half of the 1980's. These drugs have been developed using two approaches: development of partial benzodiazepine receptor agonists, and development of drugs with selectivity for the α subunit of the GABAA receptor, at which the benzodiazepine receptor binding site exists. Anxioselective drugs have been developed using the former approach, whereas sedative-selective drugs have emerged from the latter.The actions of the anxioselective drug Y-23684 and the sedative-selective drug zolpidem on the central nervous system have been studied by dual-probe microdialysis. This approach has shown that anxioselective drugs suppress accentuation of the locus coeruleus-medial prefrontal cortex norepinephrine neural activity under stress, while sedative-selective drugs suppress accentuation of the ventral tegmental area-nucleus accumbens dopamine neuron activity in the stress state. These findings suggest that the difference in the effect on the neural network relates to the selectivity for anxiolytic or sedative action.