Abstract
A novel indolamine derivative, ADN-2013, has been proved to possess a preclinical activity pro le appropriate for the treatment of behavioral and psychological symptoms of dementia. Its antidepressant and anxiolytic properties have been examined in rat and mice models. The receptor mechanisms underlying the antidepressant properties of ADN-2013 have also been elucidated. ADN-2013 signi cantly shortened the immobility time measured in the forced swim test in mice and rats, producing an e ect that was abolished by the dopamine D1-receptor antagonist SCH 23390 in rats. Moreover, ADN-2013 evoked anxiolytic-like activity in both “conditional” and “unconditional” anxiety-like paradigms in mice and rats. From these re- sults, it is likely that direct antagonism toward serotonin 5-HT6 receptors and an indirect e ect of dopamine, acting mostly via D1-like receptors, may be involved in the antidepressant action of ADN-2013. However, the partial agonist activity of ADN-2013 toward D2 receptors, observed in in vitro studies, might also contribute to this effect.