PG521

PG521 is a small molecule phosphodiesterase 10A (PDE10A) inhibitor developed by Celon Pharma S.A. for the treatment of neuropsychiatric and neurological disorders, including schizophrenia and levodopa-induced dyskinesia (LID) in Parkinson's disease. PDE10A is an enzyme primarily localized in the striatal medium spiny neurons, where it regulates the levels of the second messengers cAMP and cGMP. By inhibiting PDE10A, PG521 enhances cyclic nucleotide signaling, thereby modulating the activity of the basal ganglia circuitry. This mechanism is hypothesized to provide antipsychotic efficacy with a reduced risk of extrapyramidal side effects compared to traditional dopamine D2 receptor antagonists and to reduce motor complications in Parkinson's disease. As of early 2025, PG521 is undergoing Phase 1 clinical evaluation in healthy volunteers to characterize its safety, tolerability, and pharmacokinetic profile in comparison to the atypical antipsychotic paliperidone (PG203).