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• W4221033566 abstract "Central nervous system (CNS) disorders, such as Alzheimer's disease (AD), schizophrenia, and Parkinson's disease (PD), affect millions of people globally. However, the complex disease biology of the human brain and the lack of predictive preclinical models and disease-relevant biomarkers have significantly limited CNS drug discovery. The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding the discovery and development of CNS-directed therapeutics. It allows quantification of the distribution, expression, and modulation of the receptor under physiological and pathological conditions. Allosteric modulation of muscarinic acetylcholine receptor 4 (M4) is a new molecular mechanism that has the potential to alleviate psychosis and behavioral disturbances in dementia patients. In this chapter, we describe the discovery, in vitro , and in vivo characterization of a series of M4 positive allosteric modulators (PAMs) that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of the M4 receptor. This research eventually led to the discovery of the clinical radiotracer [ 11 C]MK-6884." @default.
• W4221033566 created "2022-04-03" @default.
• W4221033566 creator A5054566597 @default.
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• W4221033566 date "2022-03-07" @default.
• W4221033566 modified "2023-09-26" @default.
• W4221033566 title "Discovery and Potential Application of [ ¹¹ C]MK‐6884" @default.
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• W4221033566 doi "https://doi.org/10.1002/9781119627784.ch10" @default.
• W4221033566 hasPublicationYear "2022" @default.
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