PGI-7043

PGI-7043 is a potent, brain-penetrant serotonin 5-HT1B and 5-HT1D receptor agonist discovered by PsychoGenics using its proprietary SmartCube® drug discovery platform. It acts as a full agonist at human 5-HT1B and 5-HT1D receptors, with EC50 values of 1.3 nM and 0.5 nM, respectively. In preclinical rodent models, PGI-7043 has demonstrated significant anti-aggressive, antidepressant-like, and pro-social effects without inducing sedation, contrasting with traditional atypical antipsychotics like olanzapine. The compound also suppresses rapid eye movement (REM) sleep, which serves as a translational biomarker for clinical development. PGI-7043 is being investigated for the potential treatment of agitation associated with neuropsychiatric and neurodegenerative disorders, such as Alzheimer's disease, bipolar disorder, and schizophrenia, as well as social deficits in autism spectrum disorders.