Introduction: Successful phase 3 trials of KarXT in people with schizophrenia herald a new era of treating the disorder with drugs that do not target the dopamine D2 receptor. The active component of KarXT is xanomeline, a muscarinic (CHRM) M1 and M4 agonist, making muscarinic receptors a viable target for treating schizophrenia.
Areas Covered: This review covers the process of taking drugs that activate the muscarinic M1 and M4 receptors from conceptualization to the clinic and details the mechanisms by which activating the CHRM1 and 4 can affect the broad spectrum of symptoms experienced by people with schizophrenia.
Expert Opinion: Schizophrenia is a syndrome which means drugs that activate muscarinic M1 and M4 receptors, as was the case for antipsychotic drugs acting on the dopamine D2 receptor, will not give optimal outcomes in everyone within the syndrome. Thus, it would be ideal to identify people who are responsive to drugs activating the CHRM1 and 4. Given knowledge of the actions of these receptors, it is possible treatment non-response could be restricted to sub-groups within the syndrome who have deficits in cortical CHRM1 or those with one of the cognitive endophenotypes that may be identifiable by changes in the blood transcriptome.
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http://dx.doi.org/10.1080/13543784.2023.2288074 | DOI Listing |
J Nat Prod
December 2024
Key Laboratory of Chemistry in Ethnic Medicinal Resources, Ministry of Education of China, School of Ethnomedicine and Ethnopharmacy, Yunnan Minzu University, Kunming 650504, People's Republic of China.
Six undescribed macrocyclic compounds, including diarylhexanoids ( and ), a diarylhexanoid glucoside (), diarylheptanoids ( and ), and an aceroside (), were isolated from the roots of Cheval., along with 11 known analogues (-). The structures were elucidated by spectroscopic analysis, as well as by calculated optical rotatory dispersion and derivatization reactions.
View Article and Find Full Text PDFFitoterapia
December 2024
Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health. Faculty of Sciences, Mohammed First University, Oujda, BP-717, 60000 Oujda, Morocco. Electronic address:
Ethnopharmacological Relevance: Hypertension is a serious health problems and a leading cause of adult mortality worldwide. Foeniculum. vulgare Mill, a plant traditionally used for various ailments, including cardiovascular disorders such as hypertension.
View Article and Find Full Text PDFJHEP Rep
January 2025
Hepatitis Viruses and Pathobiology of Chronic Liver Diseases - LabEx DEVweCAN, Inserm U1052, Cancer Research Centre of Lyon - Hepatology Institute of Lyon F - IHU EVEREST, University of Lyon 1, ISPB, France, CNRS UMR5286, Centre Léon, Lyon, France.
Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.
View Article and Find Full Text PDFProtein Pept Lett
December 2024
Department of Pharm. Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.
Alzheimer's disease (AD) treatments currently available have ineffective results. Previously employed Acetylcholine esterase inhibitors and memantine, an NMDA receptor antagonist, target a single target structure that plays a complex role in the multifactorial progression of disease. Memantine moderates the toxic effects of excessive glutamate activity by blocking NMDA receptors, which decreases neurotoxicity in AD, while acetylcholine esterase inhibitors function by blocking cholinergic receptors (muscarinic and nicotinic), preventing the breakdown of acetylcholine, thereby enhancing cholinergic transmission, thus improving cognitive functions in mild to moderate stages of AD.
View Article and Find Full Text PDFDrugs
December 2024
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Xanomeline/trospium chloride (COBENFY™), formerly KarXT, is a first-in-class, oral, fixed-dose muscarinic agonist/antagonist combination being developed for use in schizophrenia and Alzheimer's disease psychosis. Xanomeline is thought to confer efficacy by acting as an agonist at M and M muscarinic acetylcholine receptors in the brain, and trospium chloride reduces the peripheral cholinergic adverse events associated with xanomeline. Xanomeline/trospium chloride received its first approval on 26 September 2024 in the USA for the treatment of schizophrenia in adults.
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