The Preclinical Profile of DSR-141562: A Novel Phosphodiesterase 1 Inhibitor for the Treatment of Positive Symptoms, Negative Symptoms and Cognitive Impairments Associated with Schizophrenia.

We discovered a novel orally-available and brain-penetrant phosphodiesterase 1 (PDE1) inhibitor, DSR-141562. This compound has high selectivity for the PDE1 family over other PDE families and 65 off-targets. Further, it has the preferential selectivity for predominantly brain-expressed PDE1B over other PDE1 family isoforms. Since PDE1B is believed to regulate dopaminergic and glutamatergic signal transduction, we evaluated the effects of this...