Results 11 to 20 of about 15,215 (194)

Discovery of Selective M4 Muscarinic Acetylcholine Receptor Agonists with Novel Carbamate Isosteres [PDF]

ACS Medicinal Chemistry Letters, 2019
It has been hypothesized that selective muscarinic acetylcholine receptor (mAChR) M4 subtype activation could provide therapeutic benefits to a number of neurological disorders while minimizing unwanted cholinergic side effects observed due to nonselective mAChR activation.
Qingyi Yang, Erik A. Lachapelle, Natasha M. Kablaoui, Damien Webb, Michael Popiolek, Sarah Grimwood, Rouba Kozak, Rebecca E. O’Connor, John T. Lazzaro, Christopher R. Butler, Lei Zhang   +10 more
openaire   +3 more sources

Synthesis and Evaluation of Fluorinated Peptidomimetics Enabling the Development of ¹⁸F-Labeled Radioligands Targeting Muscarinic Acetylcholine Receptor Subtype M3. [PDF]

ChemMedChem
Fluorinated peptidomimetics targeting muscarinic acetylcholine receptor subtype M3: Fluorinated peptidomimetic compounds based on a β‐alanine‐glycine scaffold, with lead compound 24 demonstrating high M3 selectivity and submicromolar potency. The first M3‐selective positron emission tomography radioligand, [18F]24, is synthesized and will be evaluated ...
Herrera-Rueda MA, Boateng MA, Wuest M, West FG, Wuest F.   +4 more
europepmc   +3 more sources

African-Specific Variability in the Acetylcholine Muscarinic Receptor M4: Association with Cocaine and Heroin Addiction [PDF]

Pharmacogenomics, 2016
This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence.The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed.Of the 20 SNPs that showed nominally significant associations, the association of the African-specific ...
Levran, Orna, Randesi, Matthew, Peles, Einat, da Rosa, Joel Correa, Ott, Jurg, Rotrosen, John, Adelson, Miriam, Kreek, Mary Jeanne   +7 more
openaire   +4 more sources

Muscarinic Acetylcholine Receptor M4 [PDF]

Definitions, 2020
openaire   +2 more sources

The potential of muscarinic M1 and M4 receptor activators for the treatment of cognitive impairment associated with schizophrenia

Frontiers in Psychiatry
Cognitive impairment is a core symptom of schizophrenia and a major determinant of poor long-term functional outcomes. Despite considerable efforts, we do not yet have any approved pharmacological treatments for cognitive impairment associated with ...
Samantha E. Yohn, Phillip D. Harvey, Stephen K. Brannan, William P. Horan, William P. Horan   +4 more
doaj   +2 more sources

Exploring Adjunctive Novel Therapeutic Approach of KarXT (Xanomeline-Trospium Chloride) for Managing Psychotic Symptoms in Patients With Schizophrenia and Alzheimer's Disease. [PDF]

Brain Behav
An overview of the mechanism of action, clinical trials, and classical findings of KarXT for the management of psychotic symptoms in patients with schizophrenia and alzheimer's disease. ABSTRACT Background Acute psychotic symptoms like delusions and hallucinations are of major concern while treating patients with schizophrenia and alzheimer's psychosis,
Kanwal A, Azeem B, Nasir H, Mumtaz F, Ashraf N, Amin MHJ, Kanwal W, Khan BW.   +7 more
europepmc   +2 more sources

Discovery of VU6025733 (AG06827): A Highly Selective, Orally Bioavailable, and Structurally Distinct M₄ Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM) with Robust <i>In Vivo</i> Efficacy. [PDF]

ACS Chem Neurosci
This work describes progress toward an M4 PAM preclinical candidate. The SAR to address potency, clearance, subtype selectivity, CNS exposure, and P-gp efflux are detailed within.
Gregro AR, Park C, Long MF, Baker LA, Bollinger KA, Ringuette AE, Peng L, Luscombe VB, Billard NB, Rodriguez AL, Niswender CM, Peng W, Dickerson JW, Rook JM, O'Neill J, Chang S, Boonen HCM, Jensen T, Thomsen MS, Bridges TM, Boutaud O, Conn PJ, Engers DW, Lindsley CW, Temple KJ.   +24 more
europepmc   +2 more sources

Downstream Signaling of Muscarinic M₄ Receptors Is Regulated by Receptor Density and Cellular Environment. [PDF]

Pharmacol Res Perspect
ABSTRACT Multiple muscarinic M4 receptor modulators are currently advancing in clinical development for the treatment of positive symptoms in schizophrenia, including agonists and positive allosteric modulators. Considering the importance of comprehending M4 receptor pharmacology for these therapeutic applications, this study investigates M4 receptor ...
Merz M, Playle C, Palchaudhuri M, Hucke O, Gross U, Ursu D.   +5 more
europepmc   +2 more sources

Rationale for Selective Muscarinic Receptor Agonists as Candidates for the Management of Cognitive and Neuropsychiatric Symptoms in Alzheimer's Disease [PDF]

Alzheimers Dement
Abstract Background Cognitive impairment and neuropsychiatric symptoms, including psychosis, are fundamental features of Alzheimer's disease (AD) and related dementias. Currently treatments for these symptoms have efficacy, safety, and tolerability limitations; new treatments with novel mechanisms are needed.
Marcus R, Vuocolo S, Ramsey I, Watson C, Kang M.   +4 more
europepmc   +2 more sources

The M4 muscarinic acetylcholine receptor positive allosteric modulator VU0467154 normalizes non‐rapid eye movement sleep deficits in non‐pathologically aged mice.

Alzheimer's & Dementia, 2023
The central cholinergic system plays an important role in normal arousal and sleep/wake architecture, and is known to decline in non‐pathological aging and Alzheimer’s disease (AD).
Jason K. Russell, Laura Wan, Shalonda Ingram, M. Bubser, C. Lindsley, Carrie K Jones   +5 more
semanticscholar   +1 more source