Pimavanserin (Nuplazid): A Comprehensive Monograph on a Novel Dopamine-Sparing Antipsychotic

Introduction and Molecular Profile

Overview and Therapeutic Distinction

Pimavanserin is a first-in-class atypical antipsychotic agent that occupies a unique position in modern psychopharmacology. It is specifically indicated for the treatment of hallucinations and delusions associated with Parkinson's Disease Psychosis (PDP), a common and debilitating non-motor symptom of Parkinson's disease.[1] Marketed under the brand name NUPLAZID® and developed by ACADIA Pharmaceuticals, pimavanserin represents a significant therapeutic advancement.[1] Its introduction addresses a critical unmet need in neurology and psychiatry, offering a treatment for psychosis that does not exacerbate the underlying motor deficits of Parkinson's disease.

The central distinction of pimavanserin lies in its novel mechanism of action. It is the first and only antipsychotic approved by the U.S. Food and Drug Administration (FDA) that is devoid of dopamine D2 receptor blocking activity.[1] For decades, the management of psychosis in patients with Parkinson's disease was a clinical paradox: conventional antipsychotics, which antagonize D2 receptors, would control psychotic symptoms at the expense of worsening parkinsonism. Pimavanserin circumvents this issue, providing a targeted therapy that alleviates hallucinations and delusions without compromising motor function, thereby marking a paradigm shift in the management of PDP.[1]

Nomenclature, Identifiers, and Physicochemical Properties

To ensure unambiguous identification, pimavanserin is characterized by a comprehensive set of names and registry numbers established throughout its development and commercialization.