Pimavanserin for bipolar disorder

Crump, C.; Litteral, Carleigh A; Elsayed, Omar H; El‐Mallakh, Rif S.

doi:10.1111/bdi.13191

Cited by 2 publications

(1 citation statement)

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“…This is notable, as pimavanserin retains efficacy in treating psychosis with a reported lack of adverse motor effects (Meltzer et al 2010, Cummings et al 2014, Fava et al 2019, Tariot et al 2021. Preliminary investigations into the use of pimavanserin for bipolar disorder have recently emerged (Crump et al 2022), highlighting the potential translational value of XOB.…”

Section: Discussionmentioning

confidence: 99%

N-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels

Denomme,

Hernandez,

Bock

et al. 2024

Mol Pharmacol

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Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical antipsychotic serotonin 2A (5-HT 2A ) receptor antagonists, such as quetiapine and olanzapine, and mood-stabilizing voltage-gated sodium channel (VGSC) blockers, such as lamotrigine, carbamazepine, and valproate, show therapeutic synergy and are often prescribed in combination for the treatment of bipolar disorder. Combination therapy is a complex task for clinicians and patients, often resulting in unexpected difficulties with dosing, drug tolerances, and decreased patient compliance. Thus, an unmet need for bipolar disorder treatment is to develop a therapeutic agent that targets both 5-HT 2A receptors and VGSCs. Towards this goal, we developed a novel small molecule that simultaneously antagonizes 5-HT 2A receptors and blocks sodium current. The new compound, N-(4-bromo-2,5-dimethoxyphenethyl)-6-(4-phenylbutoxy)hexan-1-amine (XOB) antagonizes 5-HT-stimulated, G q -mediated, calcium flux at 5-HT 2A receptors at low micromolar concentrations while displaying negligible affinity and activity at 5-HT 1A , 5-HT 2B , and 5-HT 2C receptors. At similar concentrations, XOB administration inhibits sodium current in heterologous cells and results in reduced action potential (AP) firing and VGSC-related AP properties in mouse prefrontal cortex layer V pyramidal neurons.Thus, XOB represents a new, proof-of-principle tool that can be used for future preclinical investigations and therapeutic development. This polypharmacology approach of developing a single molecule to act upon two targets, which are currently independently targeted by combination therapies, may lead to safer alternatives for the This article has not been copyedited and formatted. The final version may differ from this version.

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Section: Discussionmentioning

confidence: 99%

N-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels

Denomme,

Hernandez,

Bock

et al. 2024

Mol Pharmacol

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A New Hope in Alzheimer's Disease Psychosis: Pimavanserin

Kurhan,

Akın

2023

CAR

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Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic. There is no treatment approved by the United States Food and Drug Administration (FDA) among antipsychotics for Alzheimer’s disease Psychosis (ADP). However, pimavanserine, an atypical antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin, a new antipsychotic, will fill an important gap in this area. In clinical trials, it appears to be effective in the treatment of delusions and hallucinations at psychosis in both Parkinson's and AD. In this systematic review, we evaluated the analysis of current literature data on pimavanserin used in ADP. We searched the existing literature on clinical studies on pimavanserin therapy used in ADP. Data were determined by systematically searching PubMed, MEDLINE, EMBASE, and Google Scholar until December 2022. A total of 35 citations were found and uploaded on the Mendeley program. Abstracts and full texts of literature data were examined. Pimavanserin was observed, and satisfactory results were obtained in treating ADP. Pimavanserin has a unique mechanism of action. Pimavanserin, an atypical antipsychotic drug, has a low affinity for 5-HT2C receptors and has selective 5-HT2A reverse agonist/antagonist action. Pimavanserin has no clinically significant affinity for dopaminergic, histaminergic, muscarinic or adrenergic receptors. This agent may also achieve significant positive results in resistant psychosis treatments.

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Pimavanserin for bipolar disorder

Cited by 2 publications

References 4 publications

N-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels

N-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels

A New Hope in Alzheimer's Disease Psychosis: Pimavanserin

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