Behavioral and psychological symptoms of
dementia (BPSD) include apathy, sleep problems, irritability, wandering, elation, agitation/aggression, and
mood disorders such as depression and/or anxiety. Elderly patients are usually treated with second-generation
antipsychotics; however, they present not enough efficacy against all symptoms observed. Hence, there still is an unmet need for novel pharmacotherapeutic agents targeted BPSD. A novel arylsulfonamide derivative
ADN-1184 has been developed that possesses a preclinical profile of activity corresponding to criteria required for treatment of both
psychosis and depressive symptoms of BPSD without exacerbating
cognitive impairment or inducing motor disturbances. To broaden its pharmacological efficacy toward anxiety symptoms, its
anxiolytic properties have been examined in common animal preclinical models in rats and mice.
ADN-1184 significantly increased the number of entries into open arms measured in the elevated plus-maze test; however, it simultaneously increased parameters of exploratory activity. In the Vogel conflict drinking test,
ADN-1184 dose-dependently and significantly increased the number of shocks accepted and the number of licks. Moreover, in mice, it also had specific
anxiolytic-like activity in the four-plate test, and only negligible one at a specific mid-range dose measured in the spontaneous marble burying test. The obtained findings reveal that
ADN-1184 displays
anxiolytic-like activity in animal models of anxiety which employed punished stimuli. In its unusual combination of some
anxiolytic action with already proven
antipsychotic and
antidepressant properties, and lack of any disruptive impact on learning and memory processes and motor coordination,
ADN-1184 displays a profile that would be desired for a novel therapeutic for BPSD.