Abstract
AbstractBackgroundAlzheimer’s disease is a growing unmet medical need which involves a gradual decline in cognitive function. The therapeutic options for the treatment of cognitive disorders of this type are few with limited efficacy.MethodUsmarapride was characterized for its in‐vitro properties using binding and functional assays. Its pharmacokinetic properties were evaluated both in rats and dogs. The procognitive efficacy of usmarapride was evaluated in combination with the current standard of care used for AD type dementia. As AD is associated with comorbid depression, usmarapride was evaluated for its antidepressant like activity as well.ResultFrom in‐vitro functional studies, usmarapride was characterized as a partial agonist at 5‐hydroxytryptamine 4 (5‐HT4) receptors. It has excellent oral bio‐availability in rats and dogs. Usmarapride potentiated the procognitive effects of donepezil in behavioral animal models. Usmarapride also enhanced donepezil evoked acetylcholine levels in electroencephalogram (EEG) assay. Usmarapride was also found to have antidepressant like activity in an animal model of depression.ConclusionUsmarapride showed excellent oral efficacy in combination with donepezil in tested animal models of cognition. Additionally, usmarapride distinguish itself from currently used standard of care for the treatment of AD as it exhibits potent antidepressant like properties as well.
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