Results 1 to 10 of about 15,215 (194)

Structure-activity relationship of pyrazol-4-yl-pyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M₄. [PDF]

Acta Pharm Sin B, 2023
There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M4) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M4 positron emission tomography (PET) radioligand is currently lacking.
Haider A, Deng X, Mastromihalis O, Pfister SK, Jeppesen TE, Xiao Z, Pham V, Sun S, Rong J, Zhao C, Chen J, Li Y, Connors TR, Davenport AT, Daunais JB, Hosseini V, Ran W, Christopoulos A, Wang L, Valant C, Liang SH.   +20 more
europepmc   +3 more sources

Weight Gain With Advancing Age Is Controlled by the Muscarinic Acetylcholine Receptor M4 in Male Mice.

Endocrinology
Abstract Obesity is characterized by the excessive accumulation of adipose tissue, and it is a serious global health issue. Understanding the pathology of obesity is crucial for developing effective interventions. In this study, we investigated the role of muscarinic acetylcholine receptor M4 (mAChR-M4) in the regulation of obesity in ...
Takahashi T, Takase Y, Shiraishi A, Matsubara S, Watanabe T, Kirimoto S, Yamagaki T, Osawa M.   +7 more
europepmc   +4 more sources

Postsynaptic adaptations in direct pathway muscarinic M4-receptor signaling follow the temporal and regional pattern of dopaminergic degeneration. [PDF]

NPJ Parkinsons Dis
In Parkinson’s disease (PD), imbalances in dorsal striatum pathways are thought to lead to motor dysfunction due to loss of dopamine (DA) and the disruption of coordinated modulation with acetylcholine (ACh).
Nielsen BE, Ford CP.
europepmc   +3 more sources

The muscarinic M4 acetylcholine receptor exacerbates symptoms of movement disorders

Biochemical Society Transactions, 2023
Barbeau's seesaw hypothesis of dopamine-acetylcholine balance has predominated movement disorders literature for years. Both the simplicity of the explanation and the matching efficacy of anticholinergic treatment in movement disorders seem to support this hypothesis.
Nicole E. Chambers, Michael Millett, Mark S. Moehle   +2 more
openaire   +3 more sources

Xanomeline/trospium-induced polyuria: A patient case report. [PDF]

Ment Health Clin
Xanomeline/trospium is a newly approved agent for the management of schizophrenia. Unlike traditional antipsychotics, which are D2 receptor antagonists, xanomeline is an M1/M4 muscarinic acetylcholine receptor agonist coformulated with trospium, a ...
Leach H, DiGuglielmo F.
europepmc   +2 more sources

Identification, expression and functional characterization of M4L, a muscarinic acetylcholine M4 receptor splice variant [PDF]

PLOS ONE, 2017
Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic ...
Douglas A. Schober, Carrie H. Croy, Cara L. Ruble, Ran Tao, Christian C. Felder   +4 more
openaire   +4 more sources

Synergistic mechanisms of medullary cholinergic-serotonergic pathway interactions in regulating neuronal excitability and locomotor activities. [PDF]

Commun Biol
Medullary serotonergic (5-HT) neurons play a pivotal role in locomotor initiation. While these neurons receive cholinergic innervation, the functional consequences and underlying mechanisms remain poorly understood. Using ePet-EYFP transgenic mice (P3–P6)
Cheng Y, Dai Y, Ge R, Zhang Q.
europepmc   +2 more sources

Anti-inflammation of spirocyclopiperazinium salt compound LXM-10 targeting α7 nAChR and M4 mAChR and inhibiting JAK2/STAT3 pathway in rats. [PDF]

PLoS ONE, 2013
The present study aims to investigate the therapeutic effects of LXM-10 by intragastric administration in both acute and chronic inflammatory models, and to explore the underlying molecular mechanisms.
Weiwei Zhang, Qi Sun, Xiaoli Gao, Yimin Jiang, Runtao Li, Jia Ye   +5 more
doaj   +1 more source

Pharmacological hallmarks of allostery at the M4 muscarinic receptor elucidated through structure and dynamics

eLife, 2023
Allosteric modulation of G protein-coupled receptors (GPCRs) is a major paradigm in drug discovery. Despite decades of research, a molecular-level understanding of the general principles that govern the myriad pharmacological effects exerted by GPCR ...
Ziva Vuckovic, Jinan Wang, Vi Pham, Jesse I Mobbs, Matthew J Belousoff, Apurba Bhattarai, Wessel AC Burger, Geoff Thompson, Mahmuda Yeasmin, Vindhya Nawaratne, Katie Leach, Emma T van der Westhuizen, Elham Khajehali, Yi-Lynn Liang, Alisa Glukhova, Denise Wootten, Craig W Lindsley, Andrew Tobin, Patrick Sexton, Radostin Danev, Celine Valant, Yinglong Miao, Arthur Christopoulos, David M Thal   +23 more
doaj   +1 more source

Crystal structures of the M1 and M4 muscarinic acetylcholine receptors [PDF]

Nature, 2016
Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high ...
David M, Thal, Bingfa, Sun, Dan, Feng, Vindhya, Nawaratne, Katie, Leach, Christian C, Felder, Mark G, Bures, David A, Evans, William I, Weis, Priti, Bachhawat, Tong Sun, Kobilka, Patrick M, Sexton, Brian K, Kobilka, Arthur, Christopoulos   +13 more
openaire   +2 more sources