|Systematic (IUPAC) name|
|Metabolism||Hepatic (CYP3A4, CYP3A5, CYP2J2)|
|Biological half-life||54–56 hours|
|Molar mass||427.553 g/mol|
|(what is this?)|
Pimavanserin (INN), or pimavanserin tartate (USAN), marketed under the trade name Nuplazid, is a non-dopaminergic atypical antipsychotic developed by Acadia Pharmaceuticals for the treatment of Parkinson's disease psychosis and schizophrenia. Pimavanserin has a unique mechanism of action relative to other antipsychotics, behaving as a selective inverse agonist of the serotonin 5-HT2A receptor, with 40-fold selectivity for this site over the 5-HT2C receptor and no significant affinity or activity at the 5-HT2B receptor or dopamine receptors. The drug has met expectations for a Phase III clinical trial for the treatment of Parkinson's disease psychosis, and has completed Phase II trials for adjunctive treatment of schizophrenia alongside an antipsychotic medication.
Pimavanserin is expected to improve the effectiveness and side effect profile of antipsychotics. The results of a clinical trial examining the efficacy, tolerability and safety of adjunctive pimavanserin to risperidone and haloperidol were published in November 2012, and the results showed that pimavanserin potentiated the antipsychotic effects of subtherapeutic doses of risperidone and improved the tolerability of haloperidol treatment by reducing the incidence of extrapyramidal symptoms.
On September 2, 2014, the United States Food and Drug Administration granted Breakthrough Therapy status to Acadia's New Drug Application for pimavanserin. It was approved by the FDA to treat hallucinations and delusions associated with psychosis experienced by some people with Parkinson's disease on April 29, 2016.
Pimavanserin acts as an inverse agonist and antagonist at serotonin 5-HT2A receptors with high binding affinity (Ki 0.087 nM) and at serotonin 5-HT2C receptors with lower binding affinity (Ki 0.44 nM). Pimavanserin shows low binding to σ1 receptors (Ki 120 nM) and has no appreciable affinity (Ki >300 nM) to serotonin 5-HT2B, dopaminergic (including D2), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels.
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- Meltzer HY, Elkis H, Vanover K, Weiner DM, van Kammen DP, Peters P, Hacksell U (Nov 2012). "Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day". Schizophrenia Research 141 (2-3): 144–152. doi:10.1016/j.schres.2012.07.029. PMID 22954754.
- "ACADIA Pharmaceuticals Receives FDA Breakthrough Therapy Designation for NUPLAZID™ (Pimavanserin) for Parkinson’s Disease Psychosis". Press Releases. Acadia. 2014-09-02.
- "Press Announcements — FDA approves first drug to treat hallucinations and delusions associated with Parkinson’s disease". U.S. Food and Drug Administration. Retrieved 1 May 2016.