5‐HT1A Receptor Agonist, SUVN‐N9503012 for the Treatment of Dementia and Associated Neuropsychiatric Disorders

Abstract Background Dementia such as Alzheimer’s disease (AD) dementia is a growing unmet medical condition which involves a gradual decline in cognition and function. Few therapeutic options are available for the treatment of dementia of this type with limited efficacy. Methods SUVN‐N9503012 was characterized for its in‐vitro affinity towards 5‐hydroxytryptamine 1A (5‐HT1A) receptors using radioligand binding and functional assays. Its pharmacokinetic properties were evaluated both in rodents and dogs. The procognitive efficacy of SUVN‐N9503012 was evaluated in combination with the current standard of care (SOC), donepezil. As dementia is a co‐morbid with depression and aggression, SUVN‐N9503012 was evaluated for its potential in treating depression and agitation/aggression like behaviors. Results From in‐vitro assays, SUVN‐N9503012 was found to be a potent and selective agonist at 5‐HT1A receptors. SUVN‐N9503012 is orally bioavailable in rats and dogs and showed adequate brain penetration in rats. SUVN‐N9503012 potentiated the procognitive effects of donepezil in rat object recognition task. SUVN‐N9503012 was also found to have antidepressant like activity in rat as well as in mice in a forced swim test. SUVN‐N9503012 was found to have anti‐aggressive like activity in a mice resident‐intruder task. Conclusion From the efficacy studies carried out in combination with donepezil, we conclude that SUVN‐N9503012 has procognitive like activity in animal models of learning and memory. Apart from its procognitive like effects, SUVN‐N9503012 exhibited both anti‐depressant and anti‐aggressive like properties as well.