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Dual 5-HT and 5-HT Receptor Inverse Agonist That Affords In Vivo Antipsychotic Efficacy with Minimal hERG Inhibition for the Treatment of Dementia-Related Psychosis.
J Med Chem
August 2024
Laboratory for Medicinal Chemistry Research, Shionogi Pharmaceutical Research Center, 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
Psychosis is a distressing symptom commonly occurring in people with dementia. To treat Parkinson's disease psychosis, pimavanserin (), a 5-HT receptor inverse agonist having minimal 5-HT receptor affinity and no dopamine D receptor affinity, was approved in the United States, but not for dementia-related psychosis due to limited efficacy issues. Herein, we report on the identification of a potent and dual 5-HT and 5-HT receptor inverse agonist having minimal hERG inhibition, after having demonstrated the involvement of both 5-HT and 5-HT receptors to deliver antipsychotic efficacy in an MK-801-induced locomotor model and having conducted 5-HT and 5-HT occupancy studies including a surrogate method.
View Article and Find Full Text PDFTreatment with pimavanserin of Lewy body dementia related psychosis with previous clozapine intolerance - A case report.
Encephale
June 2024
Department of Adult Psychiatry and Addictology, Angers University Hospital, CHU of Angers, 4, rue Larrey, 49100 Angers, France. Electronic address:
Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial.
Parkinsonism Relat Disord
February 2024
Acadia Pharmaceuticals Inc., 12830 El Camino Real #400, San Diego, CA, 92130, USA. Electronic address:
Introduction: Pimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial.
Methods: This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis.
Design, Synthesis, Molecular Docking, and Biological Evaluation of Novel Pimavanserin-Based Analogues as Potential Serotonin 5-HT Receptor Inverse Agonists.
J Med Chem
July 2023
Chemistry Department, College of Science, Taibah University, Al Madinah, Al Munwarah 30002, Saudi Arabia.
There is concern for important adverse effects with use of second-generation antipsychotics in Parkinson's disease psychosis (PDP) and dementia-related psychosis. Pimavanserin is the only antipsychotic drug authorized for PDP and represents an inverse agonist of 5-HT receptors (5-HT2AR) lacking affinity for dopamine receptors. Therefore, the development of serotonin 5-HT2AR inverse agonists without dopaminergic activity represents a challenge for different neuropsychiatric disorders.
View Article and Find Full Text PDFPsychotic Disorders in the Elderly: Diagnosis, Epidemiology, and Treatment.
Psychiatr Clin North Am
December 2022
Division of Geriatric Psychiatry, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada; Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
This review covers the latest advances in our understanding of psychosis in the elderly population with respect to diagnosis, epidemiology, and treatment. Major topics of discussion include late life psychiatric disorders such as schizophrenia, schizoaffective disorder, and delusional disorder as well as dementia-related psychosis. Clinical differences between early-onset and late-onset disorders are reviewed in terms of prevalence, symptomatology, and approach to treatment.
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