Pimavanserin

Pimavanserin

Systematic (IUPAC) name
N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide
Clinical data
Trade names	Nuplazid
Legal status	US: ℞-only
Routes of administration	Oral (tablets)
Pharmacokinetic data
Protein binding	94–97%
Metabolism	Hepatic (CYP3A4, CYP3A5, CYP2J2)
Biological half-life	54–56 hours
Identifiers
CAS Number	706779-91-1 Y 706782-28-7 (tartrate)
ATC code	None
PubChem	CID: 10071196
DrugBank	DB05316
ChemSpider	8246736 N
UNII	JZ963P0DIK Y
KEGG	D08969
ChEMBL	CHEMBL2111101
Synonyms	ACP-103
Chemical data
Formula	C25H34FN3O2
Molecular mass	427.553 g/mol
SMILES CC(C)COc3ccc(cc3)CNC(=O)N(C(CC2)CCN2C)Cc(cc1)ccc1F
InChI InChI=1S/C25H34FN3O2/c1-19(2)18-31-24-10-6-20(7-11-24)16-27-25(30)29(23-12-14-28(3)15-13-23)17-21-4-8-22(26)9-5-21/h4-11,19,23H,12-18H2,1-3H3,(H,27,30) N Key:RKEWSXXUOLRFBX-UHFFFAOYSA-N N
NY (what is this?)  (verify)

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-HT_2A receptor, with 40-fold selectivity for this site over the 5-HT_2C receptor and no significant affinity or activity at the 5-HT_2B 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.

Clinical pharmacology

Pimavanserin acts as an inverse agonist and antagonist at serotonin 5-HT_2A receptors with high binding affinity (K_i 0.087 nM) and at serotonin 5-HT_2C receptors with lower binding affinity (K_i 0.44 nM). Pimavanserin shows low binding to σ₁ receptors (K_i 120 nM) and has no appreciable affinity (K_i >300 nM) to serotonin 5-HT_2B, dopaminergic (including D₂), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels.

External links

• Nuplazid (pimavanserin) Official Site