Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis. It is taken by mouth.
of pimavanserin include peripheral edema and confusion. Unlike other , pimavanserin is not a dopamine receptor antagonist, but rather is a selective antagonist or inverse agonist of the serotonin 5-HT2A receptor and to a lesser extent of the serotonin 5-HT2C receptor.
Pimavanserin was first approved for medical use in 2016. It was approved as a generic medication in 2024.
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0.087–0.5 (Ki) 1.9–50 () | |
436 (Ki) | |
0.44–10 (Ki) 91 () | |
300+ | |
300+ | |
300+ | |
300+ | |
120 | |
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: |
Pimavanserin acts as a selective inverse agonist or antagonist of the serotonin 5-HT2A receptor. It is also an antagonist or inverse agonist of the serotonin 5-HT2C receptor to a lesser extent.
The drug has an affinity (Ki) of 0.087 to 0.5nM for the serotonin 5-HT2A receptor and 0.44 to 10nM at the serotonin 5-HT2C receptor, whereas its functional inhibition () values have been reported to be 1.9nM at the serotonin 5-HT2A receptor and 91nM at the serotonin 5-HT2C receptor. Hence, it shows 3- to 50-fold greater affinity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor depending on the biological assay and 49-fold selectivity in terms of functional inhibition of the serotonin 5-HT2A receptor compared to the serotonin 5-HT2C receptor.
Pimavanserin shows low binding to σ1 receptors (Ki = 120 nM) and has no appreciable affinity (Ki > 300 nM) to serotonin 5-HT2B, dopamine (including D2), muscarinic acetylcholine, histamine, or adrenergic receptors, or to .
Pimavanserin is expected to improve the efficacy 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.
The drug met expectations for a Phase III clinical trial for the treatment of Parkinson's disease psychosis, and has completed Phase II trials for adjuvant therapy of schizophrenia alongside an antipsychotic medication.
In September 2014, the United States Food and Drug Administration (FDA) granted breakthrough therapy status to Acadia's New Drug Application for pimavanserin.
In June 2018, the FDA approved new dosages of pimavanserin to treat hallucinations and delusions associated with Parkinson's disease psychosis. A 34 mg capsule and 10 mg tablet formulation were approved. Previously, people were required to take two 17 mg tablets to achieve the recommenced 34 mg dose per day. The 10 mg dose is indicated for people also taking CYP3A4 inhibitors (e.g., ketoconazole).
In March 2024, Acadia Pharmaceuticals announced its decision to stop any further clinical trials of pimavanserin after the drug did not improve negative symptoms of schizophrenia better than placebo.
As of November 2024, a phase 2 clinical trial is underway assessing the ability of pimavanserin to trip killer of the serotonergic psychedelic psilocybin.
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